Редактирование: CD36

Platelet glycoprotein 4 (Fatty acid translocase) (FAT) (Glycoprotein IIIb) (GPIIIB) (Leukocyte differentiation antigen CD36) (PAS IV) (PAS-4) (Platelet collagen receptor) (Platelet glycoprotein IV) (GPIV) (Thrombospondin receptor) (CD36 antigen) [GP3B] [GP4]

==Publications==

{{medline-entry
|title=Liver osteopontin is required to prevent the progression of age-related nonalcoholic fatty liver disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32638492
|abstract=Osteopontin (OPN), a senescence-associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age-dependent hepatosteatosis. Thus, we investigated the role of OPN in the age-related hepatosteatosis. For this, human serum samples, animal models of aging, and cell lines in which senescence was induced were used. Metabolic fluxes, lipid, and protein concentration were determined. Among individuals with a normal liver, we observed a positive correlation between serum OPN levels and increasing age. This correlation with age, however, was absent in patients with NAFLD. In wild-type (WT) mice, serum and liver OPN were increased at 10 months old (m) along with liver p53 levels and remained elevated at 20m. Markers of liver senescence increased in association with synthesis and concentration of triglycerides ([[TG]]) in 10m OPN-deficient (KO) hepatocytes when compared to WT hepatocytes. These changes in senescence and lipid metabolism in 10m OPN-KO mice liver were associated with the decrease of 78 kDa glucose-regulated protein (GRP78), induction of ER stress, and the increase in fatty acid synthase and [[CD36]] levels. OPN deficiency in senescent cells also diminished GRP78, the accumulation of intracellular [[TG]], and the increase in [[CD36]] levels. In 20m mice, OPN loss led to increased liver fibrosis. Finally, we showed that OPN expression in vitro and in vivo was regulated by p53. In conclusion, OPN deficiency leads to earlier cellular senescence, ER stress, and [[TG]] accumulation during aging. The p53-OPN axis is required to inhibit the onset of age-related hepatosteatosis.

|keywords=* Osteopontin
* aging
* lipid metabolism
* nonalcoholic fatty liver disease
* p53
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431823
}}
{{medline-entry
|title=Reduction of senescence-associated beta-galactosidase activity by vitamin E in human fibroblasts depends on subjects' age and cell passage number.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32479666
|abstract=Cell senescence is due to the permanent cell cycle arrest that occurs as a result of the inherent limited replicative capacity toward the Hayflick limit (replicative senescence), or in response to various stressors (stress-induced premature senescence, SIPS). With the acquisition of the senescence-associated secretory phenotype (SASP), cells release several molecules (cytokines, proteases, lipids), and express the senescence-associated beta-galactosidase (SA-β-Gal). Here we tested whether vitamin E affects SA-β-Gal in an in vitro model of cell ageing. Skin fibroblasts from human subjects of different age (1, 13, 29, 59, and 88 years old) were cultured until they reached replicative senescence. At different passages (Passages 2, 9, 13, and 16), these cells were treated with vitamin E for 24 hr. Vitamin E reduced SA-β-Gal in all cells at passage 16, but at earlier passage numbers it reduced SA-β-Gal only in cells isolated from the oldest subjects. Therefore, short time treatment with vitamin E decreases SA-β-Gal in cells both from young and old subjects when reaching replicative senescence; but in cells isolated from older subjects, a decrease in SA-β-Gal by vitamin E occurs also at earlier passage numbers. The possible role of downregulation of [[CD36]] by vitamin E, a scavenger receptor essential for initiation of senescence and SASP, is discussed.

|keywords=* CD36 scavenger receptor
* alpha-tocopherol
* exosomes
* extracellular vesicles
* gene expression
* lysosome
* senescence
* signal transduction
* vitamin E
|full-text-url=https://sci-hub.do/10.1002/biof.1636
}}
{{medline-entry
|title=The age-related microglial transformation in Alzheimer's disease pathogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32408056
|abstract=Neuroinflammatory responses mediated by microglia, the resident immune cells of the central nervous system, have long been a subject of study in the field of Alzheimer's disease (AD). Microglia express a wide range of receptors that act as molecular sensors, through which they can fulfill their various functions. In this review, we first analyzed the changes in the expression levels of microglial membrane receptors SR-A, [[TREM2]], [[CD36]], [[CD33]], and CR3 in aging and AD and described the different roles of these receptors in amyloid-beta clearance and inflammatory responses. Two classical hallmarks of AD are extracellular amyloid-beta deposits and intracellular aggregated phosphorylated tau. In AD, microglia reaction was initially thought to be triggered by amyloid deposits. New evidence showed it also associated with increased phosphorylation of tau. However, which first appeared and induced activated microglia is not clear. Then we summarized diverse opinions on it. Besides, as AD is tightly linked to aging, and microglia changes dramatically on aging, yet the relative impacts of both aging and microglia are less frequently considered, so at last, we discussed the roles of aging microglia in AD. We hope to provide a reference for subsequent research.
|mesh-terms=* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Animals
* Brain
* CD36 Antigens
* Gene Expression
* Humans
* Inflammation
* Macrophage-1 Antigen
* Membrane Glycoproteins
* Microglia
* Phosphorylation
* Receptors, Immunologic
* Scavenger Receptors, Class A
* Sialic Acid Binding Ig-like Lectin 3
* tau Proteins
|keywords=* Aging
* Alzheimer's disease
* Immune response
* Microglia
* Microglial membrane receptors
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2020.03.024
}}
{{medline-entry
|title=Extracellular microparticles exacerbate oxidative damage to retinal pigment epithelial cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32173468
|abstract=Oxidative stress-induced retinal pigment epithelial cell ([[RPE]]) dysfunction is a primary contributing factor to early dry age-related macular degeneration (AMD). Oxidative injury to the retina may promote extracellular vesicles (EVs) released from [[RPE]]. In this study, we investigated the effects of oxidative-induced [[RPE]] cell-derived microparticles (RMPs) on [[RPE]] cell functions. The oxidative stress induced more RMPs released from [[RPE]] cells in vitro and in vivo, and significant more RMPs were released from aged [[RPE]] cells than that from younger [[RPE]] cells. RMPs were taken up by [[RPE]] cells in a time-dependent manner; however, blockage of [[CD36]] attenuated the uptake process. Furthermore, the decrease of [[RPE]] cell viability by RMPs treatment was associated with an increased expression of cyclin-dependent kinase inhibitors p15 and p21. RMPs enhanced senescence and interrupted phagocytic activity of [[RPE]] cells as well. The present study demonstrated that RMPs produce a strong effect of inducing [[RPE]] cell degeneration. This finding further supports the postulate that RMPs exacerbate oxidative stress damage to [[RPE]] cells, which may uncover a potentially relevant process in the genesis of dry AMD.

|keywords=* Extracellular vesicles
* Oxidative stress
* Phagocytosis
* RPE cell Dysfunction
* RPE cell-Derived microparticles (RMPs)
* Retinal pigment epithelial cell (RPE)
* Senescence
|full-text-url=https://sci-hub.do/10.1016/j.yexcr.2020.111957
}}
{{medline-entry
|title=Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32157826
|abstract=Aldehyde dehydrogenases (ALDHs) are key players in cell survival, protection, and differentiation via the metabolism and detoxification of aldehydes. ALDH activity is also a marker of stem cells. The skeletal muscle contains populations of ALDH-positive cells amenable to use in cell therapy, whose distribution, persistence in aging, and modifications in myopathic context have not been investigated yet. The Aldefluor® (ALDEF) reagent was used to assess the ALDH activity of muscle cell populations, whose phenotypic characterizations were deepened by flow cytometry. The nature of ALDH isoenzymes expressed by the muscle cell populations was identified in complementary ways by flow cytometry, immunohistology, and real-time PCR ex vivo and in vitro. These populations were compared in healthy, aging, or Duchenne muscular dystrophy ([[DMD]]) patients, healthy non-human primates, and Golden Retriever dogs (healthy vs. muscular dystrophic model, Golden retriever muscular dystrophy [GRMD]). ALDEF  cells persisted through muscle aging in humans and were equally represented in several anatomical localizations in healthy non-human primates. ALDEF  cells were increased in dystrophic individuals in humans (nine patients with [[DMD]] vs. five controls: 14.9 ± 1.63% vs. 3.6 ± 0.39%, P = 0.0002) and dogs (three GRMD dogs vs. three controls: 10.9 ± 2.54% vs. 3.7 ± 0.45%, P = 0.049). In [[DMD]] patients, such increase was due to the adipogenic ALDEF  /CD34  populations (11.74 ± 1.5 vs. 2.8 ± 0.4, P = 0.0003), while in GRMD dogs, it was due to the myogenic ALDEF  /CD34  cells (3.6 ± 0.6% vs. 1.03 ± 0.23%, P = 0.0165). Phenotypic characterization associated the ALDEF  /CD34  cells with [[CD9]], [[CD36]], CD49a, CD49c, CD49f, CD106, CD146, and CD184, some being associated with myogenic capacities. Cytological and histological analyses distinguished several ALDH isoenzymes (ALDH1A1, 1A2, 1A3, 1B1, 1L1, 2, 3A1, 3A2, 3B1, 3B2, 4A1, 7A1, 8A1, and 9A1) expressed by different cell populations in the skeletal muscle tissue belonging to multinucleated fibres, or myogenic, endothelial, interstitial, and neural lineages, designing them as potential new markers of cell type or of metabolic activity. Important modifications were noted in isoenzyme expression between healthy and [[DMD]] muscle tissues. The level of gene expression of some isoenzymes (ALDH1A1, 1A3, 1B1, 2, 3A2, 7A1, 8A1, and 9A1) suggested their specific involvement in muscle stability or regeneration in situ or in vitro. This study unveils the importance of the ALDH family of isoenzymes in the skeletal muscle physiology and homeostasis, suggesting their roles in tissue remodelling in the context of muscular dystrophies.

|keywords=* Aging
* Aldehyde dehydrogenase
* Dog model
* Duchenne muscular dystrophy
* Human
* Myogenic
* Non-human primate
* Skeletal muscle
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432589
}}
{{medline-entry
|title=Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32030468
|abstract=Remyelination following CNS demyelination restores rapid signal propagation and protects axons; however, its efficiency declines with increasing age. Both intrinsic changes in the oligodendrocyte progenitor cell population and extrinsic factors in the lesion microenvironment of older subjects contribute to this decline. Microglia and monocyte-derived macrophages are critical for successful remyelination, releasing growth factors and clearing inhibitory myelin debris. Several studies have implicated delayed recruitment of macrophages/microglia into lesions as a key contributor to the decline in remyelination observed in older subjects. Here we show that the decreased expression of the scavenger receptor [[CD36]] of aging mouse microglia and human microglia in culture underlies their reduced phagocytic activity. Overexpression of [[CD36]] in cultured microglia rescues the deficit in phagocytosis of myelin debris. By screening for clinically approved agents that stimulate macrophages/microglia, we have found that niacin (vitamin B3) upregulates [[CD36]] expression and enhances myelin phagocytosis by microglia in culture. This increase in myelin phagocytosis is mediated through the niacin receptor (hydroxycarboxylic acid receptor 2). Genetic fate mapping and multiphoton live imaging show that systemic treatment of 9-12-month-old demyelinated mice with therapeutically relevant doses of niacin promotes myelin debris clearance in lesions by both peripherally derived macrophages and microglia. This is accompanied by enhancement of oligodendrocyte progenitor cell numbers and by improved remyelination in the treated mice. Niacin represents a safe and translationally amenable regenerative therapy for chronic demyelinating diseases such as multiple sclerosis.

|keywords=* Aging
* Macrophages
* Microglia
* Oligodendrocyte progenitor cells
* Phagocytosis
* Remyelination
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181452
}}
{{medline-entry
|title=Human bone marrow adipocytes display distinct immune regulatory properties.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31327694
|abstract=The bone marrow (BM) is a major reservoir of resting memory T cells and long-lived plasma cells, capable of providing protection against recurrent infections. Whether the age-related accumulation of adipose tissue in the BM affects the functionality and maintenance of memory cells is not well understood. For the first time, we compare human femur marrow adipose tissue (fMAT) and subcutaneous white adipose tissue of the thigh (tsWAT) obtained from the same donors. Therefore, we used microarrays for comparative global gene expression analysis, and employed assays to analyse parameters of adipocyte biology, inflammation and oxidative stress. We show that fMAT adipocytes differ significantly from tsWAT adipocytes regarding specific gene expression profiles including inflammatory responses and adipogenesis/adipocyte phenotype. Concomitant with considerably lower levels of [[CD36]], a membrane-associated protein important for long-chain fatty acid uptake that is used as maturation marker, fMAT adipocytes are smaller and contain less triglycerides. fMAT adipocytes secrete similar levels of adiponectin and leptin as tsWAT adipocytes, and express increased levels of pro-inflammatory molecules concomitant with an elevated generation of reactive oxygen species (ROS) and impaired function of plasma cells in the BM. Our findings suggest that fMAT is a unique type of adipose tissue containing small adipocytes with lower [[CD36]] protein and triglyceride levels than tsWAT but high adipokine secretion. Moreover, fMAT adipocytes secrete high levels of pro-inflammatory cytokines, contributing to inflammation and impairment of plasma cell function in the BM, suggesting that fMAT has more immune regulatory functions than tsWAT.
|mesh-terms=* Adipocytes
* Aged
* Biomarkers
* Bone Marrow Cells
* CD36 Antigens
* Cytokines
* Female
* Flow Cytometry
* Fluorescent Antibody Technique
* Gene Expression Profiling
* Gene Expression Regulation
* Humans
* Immunomodulation
* Inflammation Mediators
* Male
* Middle Aged
* Oxidative Stress
* Reactive Oxygen Species
|keywords=* Aging
* Bone marrow adipocytes
* CD36
* Inflammation
* ROS
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711052
}}
{{medline-entry
|title=Expression of digestive enzyme and intestinal transporter genes during chronic heat stress in the thermally manipulated broiler chicken.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31065718
|abstract=Heat stress has a serious impact on nutrient digestion and absorption in broiler chickens. This study aimed to investigate the effects of chronic heat stress (CHS) on the mRNA expression of digestive enzymes and nutrient transporter genes in thermally manipulated (TM) broiler chickens. The evaluated genes encompassed pancreatic lipase, trypsin, amylase, maltase, and alkaline phosphatase as well as certain glucose transporter (GLUT2, SGLT1), amino acid transporter (y LAT1, CAT1), and fatty acid transporter ([[FABP1]], [[CD36]]) genes in the jejunal mucosa. Thermal manipulation was carried out at 39°C and 65% relative humidity for 18 h daily from embryonic days (ED) 10-18, while CHS was induced by raising the temperature to 35°C for 7 D throughout post-hatch days 28 to 35. After 0, 1, 3, 5, and 7 D of CHS, the pancreas and jejunal mucosa were collected from the control and TM groups to evaluate the mRNA expression by relative-quantitative real-time qRT-qPCR. Thermal manipulation significantly decreased the cloacal temperature (Tc) and the hatchling weight, and improved weight gain in broilers during post-hatch life and CHS. In addition, TM decreased the mortality rate during CHS. During CHS, the mRNA expression levels of SGLT1, GLUT2, [[FABP1]], and trypsin were significantly decreased after 1 D in control chickens, and this lower expression persisted until day 7, after which it further decreased. In contrast, in TM chickens, SGLT1, GLUT2, and [[FABP1]] expression decreased after 3, 5, and 7 D of CHS, respectively, while no significant change in trypsin expression was observed throughout the CHS period. Moreover, it was found that TM significantly modulated the mRNA expression dynamics of [[CD36]], alkaline phosphatase, y LAT1, CAT1, lipase, amylase, and maltase during CHS exposure. The findings of this study suggest that, in broiler chickens, TM has a long-lasting impact on nutrient digestion and absorption capabilities as well as Tc, mortality rates, and BW during CHS.
|mesh-terms=* Animals
* Avian Proteins
* Body Weight
* Chickens
* Cloaca
* Gastrointestinal Tract
* Gene Expression
* Hot Temperature
* Longevity
* Male
* MicroRNAs
* Random Allocation
* Reproduction
* Stress, Physiological
* Temperature
* Thermotolerance
|keywords=* broiler
* chronic heat stress
* digestive enzymes
* nutrient transporters
* thermal manipulation
|full-text-url=https://sci-hub.do/10.3382/ps/pez249
}}
{{medline-entry
|title=Pathophysiological significance of cylindromatosis in the vascular endothelium and macrophages for the initiation of age-related atherogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30554661
|abstract=Cardiovascular disease is one of the leading causes of death in the elderly, and novel therapeutic targets against atherogenesis are urgent. The initiation of atherosclerotic changes of monocyte adhesion on the vascular endothelium and subsequent foam cell formation are noteworthy pathophysiologies when searching for strategies to prevent the progression of age-related atherosclerosis. We report the significance of the deubiquitinating enzyme cylindromatosis ([[CYLD]]) in vascular remodeling by interference with inflammatory responses regulated by NF-κB signaling. The purpose of this study was to elucidate the pathological functions of [[CYLD]] in the early phase of atherogenesis associated with aging. Treatment with inflammatory cytokines induced endogenous [[CYLD]] in aortic endothelial cells (HAECs) and THP-1 cells. siRNA-mediated [[CYLD]] silencing led to enhanced monocyte adhesion along with increased adhesion molecules in HAECs treated with TNFα. In siRNA-mediated [[CYLD]] silenced RAW 264.7 macrophages treated with oxidized LDL (oxLDL), augmented lipid accumulation was observed, along with increased expression of the class A macrophage scavenger receptor (SR-A), lectin-like oxidized LDL receptor-1 (LOX-1), [[CD36]], fatty acid binding protein 4 (FABP4), the cholesterol ester synthase acyl-CoA cholesterol acyltransferase (ACAT1), MCP-1, and IL-1β and decreased expression of scavenger receptor class B type I (SR-BI). Intriguingly, [[CYLD]] gene expression was significantly reduced in bone marrow-derived macrophages of aged mice compared that of young mice, as well as in senescent HAECs compared with young cells. These findings suggest that age-related attenuation of [[CYLD]] expression in endothelial cells (ECs) and macrophages triggers the initiation of age-related atherogenesis by exacerbating monocyte adhesion on the endothelium and foam cell formation. [[CYLD]] in the vasculature may be a novel therapeutic target, especially in the early preventive intervention against the initiation of age-related atherogenesis.
|mesh-terms=* Aging
* Animals
* Atherosclerosis
* Bone Marrow Cells
* Cell Adhesion
* Cysteine Endopeptidases
* Cytokines
* Deubiquitinating Enzyme CYLD
* Endothelial Cells
* Endothelium, Vascular
* Foam Cells
* Gene Silencing
* Humans
* Inflammation Mediators
* Lipoproteins, LDL
* Macrophages
* Male
* Mice
* RAW 264.7 Cells
* RNA, Small Interfering
* THP-1 Cells
* Up-Regulation
|keywords=* Aging
* CYLD
* Endothelial cell
* Foam cell
* Inflammation
* Macrophage
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2018.12.025
}}
{{medline-entry
|title=The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30029608
|abstract=Alzheimer's disease is characterized by progressive accumulation of β-amyloid (Aβ)-containing amyloid plaques, and microglia play a critical role in internalization and degradation of Aβ. Our previous research confirmed that Nogo-66 binding to Nogo receptors (NgR) expressed on microglia inhibits cell adhesion and migration in vitro. The adhesion and migration of microglia isolated from WT and APP/PS1 mice from different ages were measured by adhesion assays and transwells. After NEP1-40 (a competitive antagonist of Nogo/NgR pathway) was intracerebroventricularly administered via mini-osmotic pumps for 2 months in APP/PS1 transgenic mice, microglial recruitment toward Aβ deposits and [[CD36]] expression were determined. In this paper, we found that aging led to a reduction of microglia adhesion and migration to fAβ  in WT and APP/PS1 mice. The adhesion and migration of microglia to fAβ  were downregulated by the Nogo, which was mediated by NgR, and the increased inhibitory effects of the Nogo could be observed in aged mice. Moreover, Rho GTPases contributed to the effects of the Nogo on adhesion and migration of microglia to fAβ  by regulating cytoskeleton arrangement. Furthermore, blocking the Nogo/NgR pathway enhanced recruitment of microglia toward Aβ deposits and expression of [[CD36]] in APP/PS1 mice. Taken together, Nogo/NgR pathway could take part in Aβ pathology in AD by modulating microglial adhesion and migration to Aβ and the Nogo/NgR pathway might be an important target for treating AD.
|mesh-terms=* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Amyloid beta-Protein Precursor
* Animals
* Brain
* Cell Adhesion
* Cell Movement
* Disease Models, Animal
* Humans
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Microglia
* Myelin Proteins
* Nogo Proteins
* Nogo Receptors
* Peptide Fragments
* Presenilin-1
* cdc42 GTP-Binding Protein
* rac1 GTP-Binding Protein
* rhoA GTP-Binding Protein
|keywords=* Adhesion
* Alzheimer’s disease
* Aβ
* Microglia
* Migration
* Nogo
* Nogo receptor
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054753
}}
{{medline-entry
|title=Cell-surface phenotyping identifies [[CD36]] and CD97 as novel markers of fibroblast quiescence in lung fibrosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29952218
|abstract=Fibroblasts play an important role in lung homeostasis and disease. In lung fibrosis, fibroblasts adopt a proliferative and migratory phenotype, with increased expression of α-smooth muscle actin (αSMA) and enhanced secretion of extracellular matrix components. Comprehensive profiling of fibroblast heterogeneity is limited because of a lack of specific cell-surface markers. We have previously profiled the surface proteome of primary human lung fibroblasts. Here, we sought to define and quantify a panel of cluster of differentiation (CD) markers in primary human lung fibroblasts and idiopathic pulmonary fibrosis (IPF) lung tissue, using immunofluorescence and FACS analysis. Fibroblast function was assessed by analysis of replicative senescence. We observed the presence of distinct fibroblast phenotypes in vivo, characterized by various combinations of Desmin, αSMA, [[CD36]], or CD97 expression. Most markers demonstrated stable expression over passages in vitro, but significant changes were observed for [[CD36]], CD54, [[CD82]], CD106, and CD140a. Replicative senescence of fibroblasts was observed from passage 10 onward. [[CD36]]- and CD97-positive but αSMA-negative cells were present in remodeled areas of IPF lungs. Transforming growth factor (TGF)-β treatment induced αSMA and collagen I expression but repressed [[CD36]] and CD97 expression. We identified a panel of stable surface markers in human lung fibroblasts, applicable for positive-cell isolation directly from lung tissue. TGF-β exposure represses [[CD36]] and CD97 expression, despite increasing αSMA expression; we therefore identified complex surface protein changes during fibroblast-myofibroblast activation. Coexistence of quiescence and activated fibroblast subtypes in the IPF lung suggests dynamic remodeling of fibroblast activation upon subtle changes to growth factor exposure in local microenvironmental niches.
|mesh-terms=* Antigens, CD
* Biomarkers
* CD36 Antigens
* Case-Control Studies
* Cell Differentiation
* Cells, Cultured
* Cellular Senescence
* Female
* Fibroblasts
* Humans
* Idiopathic Pulmonary Fibrosis
* Lung
* Male
* Middle Aged
* Receptors, G-Protein-Coupled
* Signal Transduction
|keywords=* FACS
* IPF
* cell culture
* mesenchymal marker
* replicative senescence
* surface marker
|full-text-url=https://sci-hub.do/10.1152/ajplung.00439.2017
}}
{{medline-entry
|title=An evolutionary transcriptomics approach links [[CD36]] to membrane remodeling in replicative senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29974107
|abstract=Cellular senescence, the irreversible ceasing of cell division, has been associated with organismal aging, prevention of cancerogenesis, and developmental processes. As such, the evolutionary basis and biological features of cellular senescence remain a fascinating area of research. In this study, we conducted comparative RNAseq experiments to detect genes associated with replicative senescence in two different human fibroblast cell lines and at different time points. We identified 841 and 900 genes (core senescence-associated genes) that are significantly up- and downregulated in senescent cells, respectively, in both cell lines. Our functional enrichment analysis showed that downregulated core genes are primarily involved in cell cycle processes while upregulated core gene enrichment indicated various lipid-related processes. We further demonstrated that downregulated genes are significantly more conserved than upregulated genes. Using both transcriptomics and genetic variation data, we identified one of the upregulated, lipid metabolism genes, [[CD36]], as an outlier. We found that overexpression of [[CD36]] induces a senescence-like phenotype and, further, the media of [[CD36]]-overexpressing cells alone can induce a senescence-like phenotype in proliferating young cells. Moreover, we used a targeted lipidomics approach and showed that phosphatidylcholines accumulate during replicative senescence in these cells, suggesting that upregulation of [[CD36]] could contribute to membrane remodeling during senescence. Overall, these results contribute to the understanding of evolution and biology of cellular senescence and identify several targets and questions for future studies.
|mesh-terms=* Aging
* CD36 Antigens
* Cell Cycle
* Cell Line
* Cell Membrane
* Cells, Cultured
* Cellular Senescence
* Fibroblasts
* Gene Expression Profiling
* Gene Expression Regulation
* Humans
* Lipid Metabolism
* Lipids
* Phenotype
* Selection, Genetic
* Transcriptome

|full-text-url=https://sci-hub.do/10.1039/c8mo00099a
}}
{{medline-entry
|title=Comparative analysis of endothelial cell and sub-endothelial cell elastic moduli in young and aged mice: Role of [[CD36]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29954596
|abstract=To perform comparative analysis of the role of scavenger receptor [[CD36]] on endothelial vs. sub-endothelial elastic modulus (stiffness) in the aortas of young and aged mice. Elastic moduli of endothelial and sub-endothelial layers of freshly isolated mouse aortas were quantified using atomic force microscopy. In young mice (4-6 months old), we found that while endothelial stiffness is markedly reduced in aortas of [[CD36]] mice, as compared to WT controls, no difference between [[CD36]]  and WT aortas is observed in the stiffness of the sub-endothelial layer in denuded arteries. Additionally, inhibition of myosin phosphorylation also decreases the elastic modulus in the EC, but not the sub-EC layer in WT mice. Moreover, inhibiting [[CD36]] mediated uptake of oxLDL in intact WT aortas abrogated oxLDL-induced endothelial stiffening. Further analysis of aged mice (22-25 months) revealed that aging resulted not only in significant stiffening of the denuded arteries, as was previously known, but also a comparable increase in the elastic modulus of the endothelial layer. Most significantly, this stiffening in the EC layer is dependent on [[CD36]], whereas the denuded layer is not affected. Our results show that the role [[CD36]] in stiffening of cellular components of intact aortas is endothelial-specific and that genetic deficiency of [[CD36]] protects against endothelial stiffening in aged mice. Moreover, these data suggest that endothelial stiffness in intact mouse aortas depends more on the expression of [[CD36]] than on the stiffness of the sub-endothelial layer.
|mesh-terms=* Aging
* Animals
* Arteries
* Biological Transport
* CD36 Antigens
* Elastic Modulus
* Endothelial Cells
* Lipoproteins, LDL
* Male
* Mice, Inbred C57BL
* Mice, Transgenic
* Microscopy, Atomic Force
* Myosins
|keywords=* CD36
* Endothelial and sub-endothelial stiffness
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083865
}}
{{medline-entry
|title=[[CD36]] initiates the secretory phenotype during the establishment of cellular senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29777051
|abstract=Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor [[CD36]] is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli. Moreover, ectopic [[CD36]] expression in dividing mammalian cells is sufficient to initiate the production of a large subset of the known SASP components via activation of canonical Src-p38-NF-κB signaling, resulting in the onset of a full senescent state. The secretome is further shown to be ligand-dependent, as amyloid-beta (Aβ) is sufficient to drive [[CD36]]-dependent NF-κB and SASP activation. Finally, loss-of-function experiments revealed a strict requirement for [[CD36]] in secretory molecule production during conventional senescence reprogramming. Taken together, these results uncover the Aβ-[[CD36]]-NF-κB signaling axis as an important regulator of the senescent cell fate via induction of the SASP.
|mesh-terms=* Amyloid beta-Protein Precursor
* CD36 Antigens
* Cells, Cultured
* Cellular Senescence
* Fibroblasts
* Humans
* Loss of Function Mutation
* NF-kappa B
* Signal Transduction
|keywords=* 
SASP

* aging
* amyloid‐beta
* cellular senescence
* inflammation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989758
}}
{{medline-entry
|title=Senescence Alters PPARγ (Peroxisome Proliferator-Activated Receptor Gamma)-Dependent Fatty Acid Handling in Human Adipose Tissue Microvascular Endothelial Cells and Favors Inflammation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29545239
|abstract=Adipose tissue (AT) dysfunction associated with obesity or aging is a major cause for lipid redistribution and the progression of cardiometabolic disorders. Our goal is to decipher the contribution of human AT microvascular endothelial cells (ECs) in the maintenance of fatty acid (FA) fluxes and the impact of senescence on their function. We used freshly isolated primary microvascular ECs from human AT. Our data identified the endothelial FA handling machinery including FATPs (FA transport proteins) FATP1, FATP3, FATP4, and [[CD36]] as well as [[FABP4]] (FA binding protein 4). We showed that PPARγ (peroxisome proliferator-activated receptor gamma) regulates the expression of FATP1, [[CD36]], and [[FABP4]] and is a major regulator of FA uptake in human AT EC (hATEC). We provided evidence that endothelial PPARγ activity is modulated by senescence. Indeed, the positive regulation of FA transport by PPARγ agonist was abolished, whereas the emergence of an inflammatory response was favored in senescent hATEC. This was associated with the retention of nuclear [[FOXO1]] (forkhead box protein O1), whereas nuclear PPARγ translocation was impaired. These data support the notion that PPARγ is a key regulator of primary hATEC function including FA handling and inflammatory response. However, the outcome of PPARγ activation is modulated by senescence, a phenomenon that may impact the ability of hATEC to properly respond to and handle lipid fluxes. Finally, our work highlights the role of hATEC in the regulation of FA fluxes and reveals that dysfunction of these cells with accelerated aging is likely to participate to AT dysfunction and the redistribution of lipids.
|mesh-terms=* Abdominal Fat
* Active Transport, Cell Nucleus
* Cell Proliferation
* Cells, Cultured
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p16
* Endothelial Cells
* Fatty Acid-Binding Proteins
* Fatty Acids
* Female
* Forkhead Box Protein O1
* Humans
* Inflammation
* Microvessels
* PPAR gamma
* Signal Transduction
|keywords=* adipose tissue
* cellular senescence
* endothelial cells
* fatty acids
* inflammation
* peroxisome proliferator-activated receptors
|full-text-url=https://sci-hub.do/10.1161/ATVBAHA.118.310797
}}
{{medline-entry
|title=Developmental differences between neonatal and adult human erythropoiesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29274096
|abstract=Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood (CB)- and peripheral blood (PB)-HSPC induced toward erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC. Upon in vitro erythroid differentiation, CB-derived cells proliferated 4-fold more than PB-derived cells. However, CB-derived cells exhibited a delayed kinetics of differentiation, resulting in an increased number of progenitors, notably colony-forming unit (CFU-E). The phenotypes of early erythroid differentiation stages also differed between the two sources with a significantly higher percentage of IL3R  GPA  [[CD34]]  [[CD36]]  cells generated from PB- than CB-HSPCs. This subset was found to generate both burst-forming unit (BFU-E) and CFU-E colonies in colony-forming assays. To further understand the differences between CB- and PB-HSPC, cells at eight stages of erythroid differentiation were sorted from each of the two sources and their transcriptional profiles were compared. We document differences at the [[CD34]], BFU-E, poly- and orthochromatic stages. Genes exhibiting the most significant differences in expression between HSPC sources clustered into cell cycle- and autophagy-related pathways. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis, highlighting the impact of the developmental origin of HSPCs on erythroid differentiation.
|mesh-terms=* Adult
* Aging
* Antigens, CD34
* Cells, Cultured
* Colony-Forming Units Assay
* Erythroid Precursor Cells
* Erythropoiesis
* Erythropoietin
* Fetal Blood
* Humans
* Infant, Newborn
* Transcriptome

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842122
}}
{{medline-entry
|title=Effects of high-fat diet and age on the blood lipidome and circulating endocannabinoids of female C57BL/6 mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28986283
|abstract=Alterations in lipid metabolism play a significant role in the pathogenesis of obesity-associated disorders, and dysregulation of the lipidome across multiple diseases has prompted research to identify novel lipids indicative of disease progression. To address the significant gap in knowledge regarding the effect of age and diet on the blood lipidome, we used shotgun lipidomics with electrospray ionization-mass spectrometry (ESI-MS). We analyzed blood lipid profiles of female C57BL/6 mice following high-fat diet (HFD) and low-fat diet (LFD) consumption for short (6weeks), long (22weeks), and prolonged (36weeks) periods. We examined endocannabinoid levels, plasma esterase activity, liver homeostasis, and indices of glucose tolerance and insulin sensitivity to compare lipid alterations with metabolic dysregulation. Multivariate analysis indicated differences in dietary blood lipid profiles with the most notable differences after 6weeks along with robust alterations due to age. HFD altered phospholipids, fatty acyls, and glycerolipids. Endocannabinoid levels were affected in an age-dependent manner, while HFD increased plasma esterase activity at all time points, with the most pronounced effect at 6weeks. HFD-consumption also altered liver mRNA levels of PPARα, PPARγ, and [[CD36]]. These findings indicate an interaction between dietary fat consumption and aging with widespread effects on the lipidome, which may provide a basis for identification of female-specific obesity- and age-related lipid biomarkers.
|mesh-terms=* Age Factors
* Aging
* Animals
* Diet, High-Fat
* Dietary Fats
* Endocannabinoids
* Female
* Lipid Metabolism
* Lipids
* Metabolome
* Mice
* Mice, Inbred C57BL
|keywords=* Aging
* Diet
* Electrospray ionization-mass spectrometry
* Lipidomics
* Obesity
* Phospholipids
|full-text-url=https://sci-hub.do/10.1016/j.bbalip.2017.09.011
}}
{{medline-entry
|title=Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28713239
|abstract=Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and [[CD36]] was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as [[CD68]] (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

|keywords=* Alzheimer’s disease
* aging
* microglia
* neuroinflammation
* white matter
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492660
}}
{{medline-entry
|title=Thyroid hormone-stimulated increases in [[PGC]]-1α and [[UCP2]] promote life history-specific endocrine changes and maintain a lipid-based metabolism.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27903512
|abstract=Thyroid hormones ([[TH]]s) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating [[TH]]s that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular [[TH]]-mediated activity, suggesting that in mammals naturally adapted to prolonged fasting, [[TH]]s are necessary to support metabolism. However, the functional relevance of this physiological paradox has remained largely unexplored, especially as it relates to the regulation of lipids. To address the hypothesis that TSH-mediated increase in [[TH]]s contributes to lipid metabolism, we infused early and late-fasted pups with TSH and measured several key genes in adipose and muscle, and plasma hormones associated with regulation of lipid metabolism. TSH infusion increased the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α ([[PGC]]-1α) more than 6.5-fold at 60 min in muscle, and expression of uncoupling protein 2 ([[UCP2]]) more than 27-fold during the early fast at 60 min, in adipose. Additionally, during the late fast period, the protein content of adipose [[CD36]] increased 1.1-fold, and plasma nonesterified fatty acid (NEFA) concentrations increased 25% at 120 min, with NEFA levels returning to baseline after 24 h. We show that the TSH-induced increases in [[TH]]s in fasting pups are functional and likely contribute to the maintenance of a lipid-based metabolism.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Endocrine Glands
* Fasting
* Lipid Metabolism
* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
* Seals, Earless
* Thyroid Hormones
* Uncoupling Protein 2
|keywords=* fasting
* lipids
* metabolism
* thyroid
* uncoupling protein
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336568
}}
{{medline-entry
|title=The Drosophila [[CD36]] Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27780230
|abstract=Phagocytosis is an ancient mechanism central to both tissue homeostasis and immune defense. Both the identity of the receptors that mediate bacterial phagocytosis and the nature of the interactions between phagocytosis and other defense mechanisms remain elusive. Here, we report that Croquemort (Crq), a Drosophila member of the [[CD36]] family of scavenger receptors, is required for microbial phagocytosis and efficient bacterial clearance. Flies mutant for crq are susceptible to environmental microbes during development and succumb to a variety of microbial infections as adults. Crq acts parallel to the Toll and Imd pathways to eliminate bacteria via phagocytosis. crq mutant flies exhibit enhanced and prolonged immune and cytokine induction accompanied by premature gut dysplasia and decreased lifespan. The chronic state of immune activation in crq mutant flies is further regulated by negative regulators of the Imd pathway. Altogether, our data demonstrate that Crq plays a key role in maintaining immune and organismal homeostasis.
|mesh-terms=* Aging
* Animals
* Drosophila Proteins
* Drosophila melanogaster
* Homeostasis
* Immune System
* Intestines
* Phagocytosis
* Polymerase Chain Reaction
* Receptors, Scavenger

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079587
}}
{{medline-entry
|title=Distinct inflammatory phenotypes of microglia and monocyte-derived macrophages in Alzheimer's disease models: effects of aging and amyloid pathology.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27723233
|abstract=Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid-β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte-derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in TgAPP/PS1 and TgAPP/PS1dE9, two transgenic AD mouse models, compared to WT littermates. We only found MDM infiltration in very aged mice. We determined that MDM highly expressed activation markers at basal state. In contrast, microglia exhibited an activated phenotype only with normal aging and Aβ pathology. Our study showed that [[CD14]] and [[CD36]], two receptors involved in phagocytosis, were upregulated during Aβ pathogenesis. Moreover, we observed, at the protein levels in AD models, higher production of pro-inflammatory mediators: IL-1β, p40, iNOS, CCL-3, CCL-4, and CXCL-1. Taken together, our data indicate that microglia and MDM display distinct phenotypes in AD models and highlight the specific effects of normal aging vs Aβ peptides on inflammatory processes that occur during the disease progression. These precise phenotypes of different subpopulations of myeloid cells in normal and pathologic conditions may allow the design of pertinent therapeutic strategy for AD.
|mesh-terms=* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Animals
* CD36 Antigens
* Chemokines
* Disease Models, Animal
* Encephalomyelitis, Autoimmune, Experimental
* Inflammation
* Lipopolysaccharide Receptors
* Macrophages
* Mice, Inbred C57BL
* Mice, Transgenic
* Microglia
* Models, Biological
* Monocytes
* Myeloid Cells
* Nitric Oxide Synthase Type II
* Phagocytosis
* Phenotype
* Plaque, Amyloid
|keywords=* Alzheimer's disease
* aging
* chemokines
* cytokines
* macrophages
* microglia
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242297
}}
{{medline-entry
|title=Modulation of Macrophage Polarization and [[HMGB1]]-TLR2/[[TLR4]] Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27070323
|abstract=The aim of this study was to investigate the role of macrophage polarization in aging heart. Macrophage differentiation is pathogenically linked to many inflammatory and immune disorders. It is often preceded by myocardial inflammation, which is characterized by increased cardiac damage and pro-inflammatory cytokine levels. Therefore, we investigated the hypothesis that senescence accelerated-prone (SAMP8) mice cardiac tissue would develop macrophage polarization compared with senescence-resistant control (SAMR1) mice. Both SAMP8 and SAMR1 mice were sacrificed when they became six month old. We evaluated, histo-pathological changes and modifications in protein expression by Western blotting and immuno-histochemical staining for M1 and M2 macrophage markers, high mobility group protein (HMG)B1 and its cascade proteins, pro-inflammatory factors and inflammatory cytokines in cardiac tissue. We observed significant upregulation of [[HMGB1]], toll-like receptor (TLR)2, [[TLR4]], nuclear factor (NF)κB p65, tumor necrosis factor (TNF)α, cyclooxygenase (COX)2, interferon (IFN)γ, interleukin (IL)-1β, IL-6 and M1 like macrophage specific marker cluster of differentiation (CD)68 expressions in SAMP8 heart. In contrast, M2 macrophage specific marker [[CD36]], and IL-10 expressions were down-regulated in SAMP8 mice. The results from the study demonstrated that, [[HMGB1]]-TLR2/[[TLR4]] signaling cascade and induction of phenotypic switching to M1 macrophage polarization in SAMP8 mice heart would be one of the possible reasons behind the cardiac dysfunction and thus it could become an important therapeutic target to improve the age related cardiac dysfunction. 
|mesh-terms=* Aging
* Animals
* Cyclooxygenase 2
* HMGB1 Protein
* Heart
* Inflammation
* Interleukin-10
* Interleukin-1beta
* Interleukin-6
* Macrophages
* Male
* Mice
* NF-kappa B
* Signal Transduction
* Toll-Like Receptor 2
* Toll-Like Receptor 4
* Tumor Necrosis Factor-alpha
* Up-Regulation
* Ventricular Remodeling

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829159
}}
{{medline-entry
|title=Impact of age and sex on the development of atherosclerosis and expression of the related genes in apoE deficient mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26592663
|abstract=Development of atherosclerosis is a chronic pathological process. ApoE deficient (apoE(-/-)) mice spontaneously develop atherosclerotic lesions. However, the impact of age and sex on lesions and expression of the related genes have not been fully elucidated. In this study, we collected blood and tissue samples from normal chow fed male and female apoE(-/-) mice at different ages, and determined serum lipids, [[PCSK9]] levels, en face aortic lesions and expression of some pro- or anti-atherogenic genes. We determined that lesion development was clearly associated with age, and more lesions in males than females (12.6 ± 1.7% vs. 8.9 ± 1.1% at 8 months old, P < 0.05). Associated with age, serum total, LDL- and HDL-cholesterol and [[PCSK9]] levels increased with more [[PCSK9]] in females than males (313 ± 31 ng/mL vs. 239 ± 28 ng/mL at 8 months old, P < 0.05); expression of liver [[LDLR]] and [[ABCA1]] decreased while of SR-BI increased; expression of macrophage [[ABCA1]] and SR-BI decreased but of [[CD36]] increased. Estrogen and tamoxifen induced [[ABCA1]] and SR-BI expression, respectively, in macrophages isolated from female mice at the different age. Taken together, our study suggests that aging facilitates lesion development in apoE(-/-) mice with greater effect on male mice. The lesion development is also related to expression of pro- or anti-atherogenic genes in tissues, particularly in macrophages. 
|mesh-terms=* ATP Binding Cassette Transporter 1
* Aging
* Animals
* Apolipoproteins E
* Atherosclerosis
* CD36 Antigens
* Female
* Lipids
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Sex Characteristics
|keywords=* ABCA1
* Age
* Atherosclerosis
* CD36
* Sex
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2015.11.064
}}
{{medline-entry
|title=Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24760536
|abstract=Recent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (n=12) or placebo (n=13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting. Despite an increase in lipid oxidation (P<0.05), testosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, [[PRKAA2]], and PRKAG3), OxPhos (NDUFS1, [[ETFA]], [[SDHA]], [[UQCRC1]], and COX5B), or lipid metabolism (ACADVL, [[CD36]], [[CPT1B]], [[HADH]], and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear ([[SDHA]] and [[UQCRC1]]) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy. The beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.
|mesh-terms=* Aging
* Blotting, Western
* Body Composition
* Electrophoresis, Polyacrylamide Gel
* Lipid Metabolism
* Muscle, Skeletal
* Oxidative Phosphorylation
* Real-Time Polymerase Chain Reaction
* Testosterone

|full-text-url=https://sci-hub.do/10.1530/EJE-14-0006
}}
{{medline-entry
|title=Increased hepatic [[CD36]] expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24751397
|abstract=[[CD36]] has been associated with obesity and diabetes in human liver diseases, however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is unknown. Therefore, liver biopsies were collected from individuals with histologically normal livers (n=30), and from patients diagnosed with simple steatosis (NAS; n=26). Patients were divided into two groups according to age and liver biopsy samples were immunostained for [[CD36]]. NAFLD parameters were examined in young (12-week) and middle-aged (52-week) C57BL/6J mice, some fed with chow-diet and some fed with low-fat (LFD; 10% kcal fat) or high-fat diet (HFD; 60% kcal fat) for 12-weeks. [[CD36]] expression was positively associated with age in individuals with normal livers but not in NAS patients. However, [[CD36]] was predominantly located at the plasma membrane of hepatocytes in aged NAS patients as compared to young. In chow-fed mice, aging, despite an increase in hepatic [[CD36]] expression, was not associated with the development of NAFLD. However, middle-aged mice did exhibit the development of HFD-induced NAFLD, mediated by an increase of [[CD36]] on the membrane. Enhanced [[CD36]]-mediated hepatic fat uptake may contribute to an accelerated progression of NAFLD in mice and humans. Therapies to prevent the increase in [[CD36]] expression and/or [[CD36]] from anchoring at the membrane may prevent the development of NAFLD. 
|mesh-terms=* Adult
* Aged
* Aging
* Animals
* CD36 Antigens
* Cell Membrane
* Female
* Hepatocytes
* Humans
* Immunoblotting
* Immunohistochemistry
* Liver
* Male
* Mice
* Mice, Inbred C57BL
* Middle Aged
* Non-alcoholic Fatty Liver Disease
* Real-Time Polymerase Chain Reaction
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032795
}}
{{medline-entry
|title=Long-term vitamin E supplementation reduces atherosclerosis and mortality in Ldlr-/- mice, but not when fed Western style diet.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24529144
|abstract=Epidemiological and experimental evidence have indicated potential health benefits of vitamin E supplementation on coronary heart disease (CHD), but several clinical trials have reported no benefit from vitamin E supplementation on CHD. We hypothesized that supplemental intake of vitamin E from an early age may prevent or retard the development and progression of atherosclerosis and CHD mortality. To test this hypothesis, 300 Ldlr(-/-) mice were divided into groups receiving Western style high fat/cholesterol (HFHC), moderate fat/cholesterol (MFMC), or low fat/cholesterol (LFLC) diets all containing 50 IU of vitamin E. These dietary groups were further subdivided into four sub-groups (n = 25) receiving their respective diets with no vitamin E supplementation or additionally supplemented with vitamin E (500 IU/kg diet) starting at the early age of 5 wks, or 6 mo, or 12 mo. All mice remained on their assigned diets until age 18 mo. Body weight, health status and survival rate of mice were monitored and recorded. After 18 mo of dietary treatments, mice were sacrificed. Body weight was the highest in HFHC groups and the lowest in LFLC groups. Plasma concentration of cholesterol and triglycerides was high in all dietary groups, and plasma vitamin E was high in vitamin E supplemented groups. Fifty percent of mice fed Western style HFHC diet and 53% of mice fed MFMC diet survived during the 18 mo, whereas 75% of mice fed LFLC diet survived during the 18 mo dietary treatments. At the age of 18 mo, all the Ldlr(-/-) mice, regardless of dietary treatments, had several advanced atherosclerotic lesions in both aortic root and aortic tree. Within the LFLC groups, those that received vitamin E supplements from age 5 wks up to 18 mo had a significantly higher survival rate of 88% (p = 0.04) and lower mortality (12%) compared to mice that did not receive vitamin E supplements (64%). This lower mortality rate and higher survival rate coincided with significantly (p = 0.03) fewer aortic lesions in the vitamin E supplemented LFLC group (50%) compared to LFLC mice that did not receive vitamin E supplements in their diets (65%). Subjective immunohistochemical evaluation of aortic valves showed that LFLC mice that received vitamin E supplements for 18 mo had less intima media thickness compared to LFLC mice that did not receive vitamin E supplements in their diet. The LFLC mice that were supplemented with vitamin E for 18 mo had the lowest mRNA expression of inflammatory markers such as VCAM-1, MCP-1 and [[CD36]] in samples obtained from lesion and non-lesionareas. In conclusion, 500 mg vitamin E/kg diet in Ldlr(-/-) mice is not effective at reducing mortality and atherosclerosis when the diet contained high or medium levels of fat and cholesterol. However, a relatively low dose and long-term vitamin E supplementation started from an early age is effective in reducing mortality and atherosclerotic lesions in genetically prone Ldlr(-/-) mice fed LFLC diet.
|mesh-terms=* Aging
* Animals
* Atherosclerosis
* Cholesterol, Dietary
* Diet
* Diet, High-Fat
* Dietary Fats
* Dietary Supplements
* Lipids
* Male
* Mice
* Receptors, LDL
* Vitamin E
|keywords=* Atherosclerosis
* Fatty lesion
* Ldlr(−/−) mouse
* Long-term supplementation
* Survival
* Vitamin E
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028145
}}
{{medline-entry
|title=Hepatic menin recruits [[SIRT1]] to control liver steatosis through histone deacetylation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23867312
|abstract=The development and progression of non-alcoholic fatty liver disease are associated with aging, obesity, and type 2 diabetes. Understanding the precise regulatory networks of this process will contribute to novel therapeutic strategies. Hepatocyte-specific Men1 knockout mice were generated using Cre/loxP technology. Lipid and glucose metabolic phenotypes and mechanisms were investigated in aging and high-fat diet fed mice. The expression of menin, encoded by multiple endocrine neoplasia 1 (Men1) gene, is reduced in the liver of aging mice. Hepatocyte-specific deletion of Men1 induces liver steatosis in aging mice. Menin deficiency promotes high-fat diet-induced liver steatosis in mice. Menin recruits [[SIRT1]] to control hepatic [[CD36]] expression and triglyceride accumulation through histone deacetylation. Our work reveals that the adaptor protein menin is critical for the progression of hepatic steatosis during aging and metabolic imbalance.
|mesh-terms=* Acetylation
* Aging
* Animals
* CD36 Antigens
* Diet, High-Fat
* Fatty Liver
* Glucose
* Histones
* Liver
* Mice
* Mice, Inbred C57BL
* Proto-Oncogene Proteins
* Sirtuin 1
|keywords=* Aging
* HFD
* Histone deacetylation
* IPGTT
* ITT
* LMKO
* Liver steatosis
* MEN1
* Menin
* NAFLD
* SIRT1
* Scd-1
* TC
* TG
* high-fat diet
* insulin tolerance tests
* intra-peritoneal glucose tolerance tests
* liver-specific Men1 knockout mice
* multiple endocrine neoplasia type 1
* non-alcoholic fatty liver disease
* stearoyl CoA desaturase-1
* total cholesterol
* triglyceride
|full-text-url=https://sci-hub.do/10.1016/j.jhep.2013.07.011
}}
{{medline-entry
|title=Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23206327
|abstract=The intricate interactions between the immune, endocrine and central nervous systems shape the innate immune response of the brain. We have previously shown that estradiol suppresses expression of immune genes in the frontal cortex of middle-aged ovariectomized rats, but not in young ones reflecting elevated expression of these genes in middle-aged, ovarian hormone deficient animals. Here, we explored the impact of menopause on the microglia phenotype capitalizing on the differential expression of macrophage-associated genes in quiescent and activated microglia. We selected twenty-three genes encoding phagocytic and recognition receptors expressed primarily in microglia, and eleven proinflammatory genes and followed their expression in the rat frontal cortex by real-time PCR. We used young, middle-aged and middle-aged ovariectomized rats to reveal age- and ovariectomy-related alterations. We analyzed the expression of the same set of genes in the postcentral and superior frontal gyrus of pre- and postmenopausal women using raw microarray data from our previous study. Ovariectomy caused up-regulation of four classic microglia reactivity marker genes including Cd11b, Cd18, Cd45 and Cd86. The change was reversible since estradiol attenuated transcriptional activation of the four marker genes. Expression of genes encoding phagocytic and toll-like receptors such as Cd11b, Cd18, [[C3]], Cd32, Msr2 and Tlr4 increased, whereas scavenger receptor Cd36 decreased following ovariectomy. Ovarian hormone deprivation altered the expression of major components of estrogen and neuronal inhibitory signaling which are involved in the control of microglia reactivity. Strikingly similar changes took place in the postcentral and superior frontal gyrus of postmenopausal women. Based on the overlapping results of rat and human studies we propose that the microglia phenotype shifts from the resting toward the reactive state which can be characterized by up-regulation of CD11b, [[CD14]], CD18, CD45, [[CD74]], [[CD86]], [[TLR4]], down-regulation of [[CD36]] and unchanged [[CD40]] expression. As a result of this shift, microglial cells have lower threshold for subsequent activation in the forebrain of postmenopausal women.
|mesh-terms=* Adult
* Age Factors
* Aged
* Aging
* Animals
* Antigens, CD
* Cytokines
* Estradiol
* Estrogen Receptor alpha
* Female
* Frontal Lobe
* Gene Expression Regulation
* Histocompatibility Antigens
* Humans
* Menopause
* Middle Aged
* Ovariectomy
* Phagocytosis
* RNA, Messenger
* Rats
* Rats, Wistar
* Toll-Like Receptor 4
* Toll-Like Receptor 9

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558453
}}
{{medline-entry
|title=[[CD36]] expression in the brains of SAMP8.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22884668
|abstract=SAMP8, senescence accelerated mice with age-related deficits in memory and learning, are known to show age-related increases of amyloid precursor protein (APP) and immunopositivity for amyloid-β (Aβ) proteins, and moreover to be under elevated oxidative stress. The elevated expression of class B scavenger receptor [[CD36]], which is the receptor of oxidized LDL and also one of efflux transporters of Aβ proteins in the cerebral vessels, is thought to mediate free radical production in cerebral ischemia and induce oxidative stress. Accordingly, by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical techniques, we examined whether the expression of [[CD36]] was increased in the brains of 10-12-week-old SAMP8 with elevated oxidative stress. Ten to 12-week-old SAMR1 mice were used as controls without the features. The gene and protein expression of [[CD36]] was significantly higher in the brains of SAMP8 than those of SAMR1. Confocal microscopic examination revealed that the [[CD36]] immunoreactivity was seen in the cytoplasm of endothelial cells and F4/80-positive perivascular cells of the brains. These findings indicate that the expression of [[CD36]] in the brains of SAMP8 is increased compared with that of SAMR1.
|mesh-terms=* Aging
* Animals
* Blotting, Western
* Brain
* CD36 Antigens
* Male
* Mice
* Mice, Inbred Strains
* Microscopy, Confocal
* Oxidative Stress
* Real-Time Polymerase Chain Reaction
* Reverse Transcriptase Polymerase Chain Reaction

|full-text-url=https://sci-hub.do/10.1016/j.archger.2012.07.007
}}
{{medline-entry
|title=Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22342341
|abstract=We previously reported that the anti-inflammatory cytokine interleukin (IL)-4 induced selective clearance of oligomeric β-amyloid (Aβ(1-42)) in rat primary type 2 microglial cells. For the present study, we investigated whether IL-4 and IL-13 could activate microglial cells to induce Aβ clearance in vivo and improve cognitive deficits in APP23 mice, which are amyloid precursor protein transgenic mice. We administered an intracerebral microinjection of a mixture of IL-4 and IL-13 or of saline vehicle into one hemisphere of APP23 mice and their wild-type littermates, 4.5 and 9 months old, after which we evaluated the effects of these treatments on spatial learning and memory by Morris Water Maze test and on accumulated amounts of Aβ. The cytokine injection significantly improved memory deficits of 4.5-month-old APP23 mice, but did not do so in 9-month-old APP23 mice, even though similar Aβ reductions were observed in both age groups of APP23 mice in the ipsilateral neocortex. The cytokine injection improved memory impairment of 9-month-old wild-type (WT) mice in the probe trial. Immunohistochemical analysis of the 4.5-month-old APP23 mice revealed the presence of increased numbers of microglial cells at 2 days after the cytokine injection. In addition to induced [[CD36]] expression in the activated microglia, increased expression of neprilysin, mainly in neurons, suggested that the cytokines improved the cognitive deficits via degradation and clearance of intra- and extraneuronal Aβ peptides, of buffer-extractable nonplaque form. Double immunostaining also revealed that most of the activated microglia had the M2-like phenotype. This unique mechanism of IL-4/IL-13-induced clearance of Aβ may provide an additional strategy to prevent and/or cure Alzheimer's disease at early stage.
|mesh-terms=* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Animals
* Cognition Disorders
* Disease Models, Animal
* Humans
* Injections, Intraventricular
* Interleukin-13
* Interleukin-4
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Microinjections
* Plaque, Amyloid

|full-text-url=https://sci-hub.do/10.1016/j.neuroscience.2012.01.049
}}
{{medline-entry
|title=Reactivation of peroxisome proliferator-activated receptor alpha in spontaneously hypertensive rat: age-associated paradoxical effect on the heart.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21654328
|abstract=Prevention of left ventricular hypertrophy remains a challenge in the prevention of hypertension-induced adverse cardiac remodeling. Cardiac hypertrophy is associated with a shift in energy metabolism from predominantly fatty acid to glucose with a corresponding reduction in the expression of fatty acid oxidation enzyme genes. Although initially adaptive, the metabolic switch seems to be detrimental in the long run. This study was taken up with the objective of examining whether the stimulation of fatty acid oxidation by the activation of peroxisome proliferator-activated receptor alpha (PPARα), a key regulator of fatty acid metabolism, can prevent cardiac hypertrophy. Fenofibrate was used as the PPARα agonist. Spontaneously hypertensive rats (SHRs) in the initial stages of hypertrophy (2 months) and those with established hypertrophy (6 months) were treated with fenofibrate (100 mg·kg·d for 60 days). Cluster of differentiation 36 ([[CD36]])-responsible for myocardial fatty acid uptake, carnitine palmitoyl transferase 1β-a mitochondrial transporter protein and medium chain acyl-Co-A dehydrogenase-a key enzyme in beta oxidation of fatty acids were selected as indicators of fatty acid metabolism. Hypertrophy was apparent at 2 months and metabolic shift at 4 months of age in SHRs. The treatment prevented cardiac remodeling in young animals but aggravated hypertrophy in older animals. Hypertrophy showed a positive association with malondialdehyde levels and cardiac NF-κB gene expression, signifying the role of oxidative stress in the mediation of hypertrophy. Expression of carnitine palmitoyl transferase 1β and medium chain acyl-Co-A dehydrogenase was upregulated on treatment. However, [[CD36]] showed an age-dependent variation on treatment, with no change in expression in young rats and downregulation in older animals. It is inferred that the stimulation of PPARα before the initiation of metabolic remodeling may prevent cardiac hypertrophy, but reactivation after the metabolic adaptation aggravates hypertrophy. Whether the downregulation of [[CD36]] is mediated by decreased substrate availability remains to be explored. Age-dependent paradoxical effect on the heart in response to fenofibrate, used as a lipid-lowering drug, can have therapeutic implications.
|mesh-terms=* Aging
* Animals
* Azo Compounds
* Blood Pressure
* Body Weight
* Cholesterol
* Disease Models, Animal
* Energy Metabolism
* Fatty Acids
* Fenofibrate
* Gene Expression
* Heart
* Hypertension
* Hypertrophy, Left Ventricular
* Hypolipidemic Agents
* Lipid Peroxidation
* Male
* Myocytes, Cardiac
* Oxidative Stress
* PPAR alpha
* Rats
* Rats, Inbred SHR
* Rats, Wistar
* Time Factors
* Ventricular Remodeling

|full-text-url=https://sci-hub.do/10.1097/FJC.0b013e31822368d7
}}
{{medline-entry
|title=Increased [[CD36]] expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21387178
|abstract=As aging is a significant risk factor for the development of left ventricular hypertrophy and cardiovascular disease, we hypothesized that hearts from middle-aged mice may be more sensitive to the effects of a high fat (HF) diet than hearts from young mice. To investigate this, young (10-12 week old) and middle-aged (40-44 week old) male mice were fed a low fat (LF) or HF diet (10 or 60 kcal% fat, respectively) for 12 weeks. Following this 12-week period, we show that [[CD36]] protein expression was not changed in hearts from young mice yet was increased 1.5-fold in the middle-aged HF group compared with LF-fed age-matched counterparts. Correlated with increased [[CD36]] expression, middle-aged mice displayed a greater degree of cardiac hypertrophy compared with young mice when fed a HF diet, and this was observed in the absence of cardiac dysfunction. Furthermore, middle-aged [[CD36]] knockout mice were protected against HF diet-induced cardiac hypertrophy, supporting a link between [[CD36]] and cardiac hypertrophy. To further explore potential mechanisms that may explain why middle-aged mice are more susceptible to HF diet-induced cardiac hypertrophy, we investigated mediators of cardiac growth. We show that myocardial ceramide levels were significantly increased in middle-aged mice fed a HF diet compared with LF-fed controls, which was also correlated with inhibition of AMP-activated protein kinase (AMPK). Consistent with AMPK being a negative regulator of cardiac hypertrophy, decreased AMPK activity also resulted in the activation of the mTOR/p70S6K pathway, which is known to enhance protein synthesis associated with cardiac hypertrophy. Together, these data suggest that increased myocardial [[CD36]] expression in hearts from middle-aged mice may contribute to HF diet-induced cardiac hypertrophy and that this may be mediated by elevated ceramide levels signaling through AMPK. Overall, we suggest that inhibition of [[CD36]]-mediated fatty acid uptake may prevent obesity-related cardiomyopathies in the middle-aged population.
|mesh-terms=* AMP-Activated Protein Kinases
* Aging
* Animals
* CD36 Antigens
* Cardiomegaly
* Cardiomyopathies
* Dietary Fats
* Immunoblotting
* Male
* Mice
* Obesity

|full-text-url=https://sci-hub.do/10.1007/s00109-010-0720-4
}}
{{medline-entry
|title=[[CD36]] plays an important role in the clearance of oxLDL and associated age-dependent sub-retinal deposits.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21098885
|abstract=Age-related macular degeneration (AMD) represents the major cause of vision loss in industrialized nations. Laminar deposits in Bruch's membrane (BM) are among the first prominent histopathologic features, along with drusen formation, and have been found to contain oxidized lipids. Increases in concentrations of oxidized LDL (oxLDL) in plasma are observed with age and high fat high (HFHC) cholesterol diet. [[CD36]] is the principal receptor implicated in uptake of oxLDL, and is expressed in the retinal pigment epithelium ([[RPE]]). We determined if [[CD36]] participates in oxLDL uptake in [[RPE]] and correspondingly in clearance of sub-retinal deposits. Uptake of oxLDL by [[RPE]]in vitro and in vivo was [[CD36]]-dependent. [[CD36]] deficiency in mice resulted in age-associated accumulation of oxLDL and sub-retinal BM thickening, despite fed a regular diet. Conversely, treatment of HFHC-fed ApoE null mice with a [[CD36]] agonist, EP80317 (300 μg/kg/day), markedly diminished thickening of BM, and partially preserved (in part) photoreceptor function. In conclusion, our data uncover a new role for [[CD36]] in the clearance of oxidized lipids from BM and in the prevention of age-dependent sub-retinal laminar deposits.
|mesh-terms=* Age Factors
* Aging
* Animals
* Apolipoproteins E
* Bruch Membrane
* CD36 Antigens
* Cells, Cultured
* Dietary Fats
* Disease Models, Animal
* Lipoproteins, LDL
* Macular Degeneration
* Mice
* Mice, Knockout
* Oligopeptides
* Retinal Pigment Epithelium

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034186
}}
{{medline-entry
|title=Stromal stem cells from adipose tissue and bone marrow of age-matched female donors display distinct immunophenotypic profiles.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20857424
|abstract=Adipose tissue is composed of lipid-filled mature adipocytes and a heterogeneous stromal vascular fraction (SVF) population of cells. Similarly, the bone marrow (BM) is composed of multiple cell types including adipocytes, hematopoietic, osteoprogenitor, and stromal cells necessary to support hematopoiesis. Both adipose and BM contain a population of mesenchymal stromal/stem cells with the potential to differentiate into multiple lineages, including adipogenic, chondrogenic, and osteogenic cells, depending on the culture conditions. In this study we have shown that human adipose-derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) populations display a common expression profile for many surface antigens, including CD29, CD49c, CD147, CD166, and HLA-abc. Nevertheless, significant differences were noted in the expression of [[CD34]] and its related protein, [[PODXL]], [[CD36]], CD 49f, CD106, and CD146. Furthermore, ASCs displayed more pronounced adipogenic differentiation capability relative to BMSC based on Oil Red staining (7-fold vs. 2.85-fold induction). In contrast, no difference between the stem cell types was detected for osteogenic differentiation based on Alizarin Red staining. Analysis by RT-PCR demonstrated that both the ASC and BMSC differentiated adipocytes and osteoblast displayed a significant upregulation of lineage-specific mRNAs relative to the undifferentiated cell populations; no significant differences in fold mRNA induction was noted between ASCs and BMSCs. In conclusion, these results demonstrate human ASCs and BMSCs display distinct immunophenotypes based on surface positivity and expression intensity as well as differences in adipogenic differentiation. The findings support the use of both human ASCs and BMSCs for clinical regenerative medicine.
|mesh-terms=* Adipogenesis
* Adipose Tissue
* Adult
* Aging
* Bone Marrow Cells
* Cell Lineage
* Cells, Cultured
* Female
* Humans
* Immunophenotyping
* Mesenchymal Stem Cells
* Osteogenesis
* RNA, Messenger
* Stromal Cells
* Tissue Donors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340690
}}
{{medline-entry
|title=Alterations in skeletal muscle fatty acid handling predisposes middle-aged mice to diet-induced insulin resistance.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20299464
|abstract=Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to investigate how middle age impacts skeletal muscle fatty acid handling and to determine how this contributes to the development of diet-induced insulin resistance. Whole-body and skeletal muscle insulin resistance were studied in young and middle-aged wild-type and [[CD36]] knockout (KO) mice fed either a standard or a high-fat diet for 12 weeks. Molecular signaling pathways, intramuscular triglycerides accumulation, and targeted metabolomics of in vivo mitochondrial substrate flux were also analyzed in the skeletal muscle of mice of all ages. Middle-aged mice fed a standard diet demonstrated an increase in intramuscular triglycerides without a concomitant increase in insulin resistance. However, middle-aged mice fed a high-fat diet were more susceptible to the development of insulin resistance-a condition that could be prevented by limiting skeletal muscle fatty acid transport and excessive lipid accumulation in middle-aged [[CD36]] KO mice. Our data provide insight into the mechanisms by which aging becomes a risk factor for the development of insulin resistance. Our data also demonstrate that limiting skeletal muscle fatty acid transport is an effective approach for delaying the development of age-associated insulin resistance and metabolic disease during exposure to a high-fat diet.
|mesh-terms=* Aging
* Animal Feed
* Animals
* Basal Metabolism
* CD36 Antigens
* Calorimetry, Indirect
* Fatty Acids
* Insulin Resistance
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Muscle, Skeletal
* Obesity

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874697
}}
{{medline-entry
|title=Elevated expression of the metabolic regulator receptor-interacting protein 140 results in cardiac hypertrophy and impaired cardiac function.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20083575
|abstract=Receptor-interacting protein 140 (RIP140) is a ligand-dependent cofactor for nuclear receptors that regulate networks of genes involved in cellular processes, including metabolism. An important role for RIP140 in metabolic control has been identified in RIP140 null mice, whose phenotypes include derepression of genes involved in energy mobilization or catabolism in adipocytes and a switch to more oxidative fibres in skeletal muscle. We hypothesized that ubiquitous expression of RIP140 would suppress metabolic processes, leading to defects in development or cellular function. The primary effect of exogenous expression of RIP140 mRNA (real-time PCR) and protein (western blotting) in transgenic mice is impaired postnatal heart function. There was rapid onset of cardiac hypertrophy and ventricular fibrosis, detected microscopically, in male RIP140 transgenic mice from 4 weeks of age, resulting in 25% mortality by 5 months. RIP140 exogenous expression in the heart leads to decreased mitochondria state III and state IV membrane potential and oxygen consumption. Quantitative PCR showed more than 50% reduced expression of genes involved in mitochondrial activity and fatty acid metabolism, including mitochondrial transcription factor A, cytochrome oxidase VIIa, cytochrome XII, [[CD36]], medium-chain acyl dehydrogenase, and fatty acid transport protein, many of which are known targets for nuclear receptors, including peroxisome proliferator-activated receptors PPARalpha and PPARdelta and oestrogen-related receptors ERRalpha and ERRgamma. This study demonstrates that RIP140 is an important cofactor in postnatal cardiac function and that inhibition of the action of RIP140 may provide a model system to investigate specific interventions designed to prevent or delay the onset of cardiac disease.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Aging
* Animals
* Cardiomegaly
* Energy Metabolism
* Female
* Fibrosis
* Gene Expression Regulation
* Gene Regulatory Networks
* Genotype
* Heart Atria
* Heart Ventricles
* Humans
* Magnetic Resonance Imaging
* Male
* Membrane Potential, Mitochondrial
* Mice
* Mice, Transgenic
* Mitochondria, Heart
* Myocardial Contraction
* Myocardium
* Nuclear Proteins
* Nuclear Receptor Interacting Protein 1
* Oxygen Consumption
* Phenotype
* RNA, Messenger
* Sex Factors

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868176
}}
{{medline-entry
|title=Genetic ablation of [[CD36]] induces age-related corneal neovascularization.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18812768
|abstract=Corneal avascularity is tightly regulated by a balance between angiogenic and antiangiogenic factors (angiogenic privilege). In the current study, we tested the hypothesis that the [[CD36]] /  antiangiogenic receptor contributes toward the maintenance of corneal avascularity. Corneas of [[CD36]] wild-type ([[CD36]]) and knockout ([[CD36]]) mice aged 4, 16, 52, and 78 weeks were histologically evaluated for corneal haze and neovascularization (NV). Quantitative real-time polymerase chain reaction was performed on corneal tissue from [[CD36]] /  and [[CD36]]-/- mice aged 4 and 52 weeks to examine the effect of [[CD36]] deficiency on expression of relevant angiogenic factors. Corneal haze and NV were absent in [[CD36]] /  mice at all ages. Conversely, corneal haze and NV were evident at 52 and 78 weeks in [[CD36]]-/- mice, and the latter demonstrated a significant increase in vessel density at 52 and 78 weeks. Interestingly, compared with [[CD36]] /  mice, in the corneas of 52-week-old [[CD36]]-/- mice, thrombospondin-1 messenger RNA was repressed, and vascular endothelial growth factor A, c-Jun N-terminal kinase-1, and c-Jun levels were robustly upregulated. [[CD36]]-/- mice develop corneal NV that increases in severity with age, thus accentuating the role of [[CD36]] in preserving corneal avascularity.
|mesh-terms=* Aging
* Animals
* Blood Vessels
* CD36 Antigens
* Cornea
* Corneal Neovascularization
* Corneal Opacity
* Down-Regulation
* Gene Deletion
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Mitogen-Activated Protein Kinase 8
* Proto-Oncogene Proteins c-jun
* RNA, Messenger
* Thrombospondin 1
* Up-Regulation
* Vascular Endothelial Growth Factor A

|full-text-url=https://sci-hub.do/10.1097/ICO.0b013e31817780b6
}}
{{medline-entry
|title=Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18701698
|abstract=Early microglial accumulation in Alzheimer's disease (AD) delays disease progression by promoting clearance of beta-amyloid (Abeta) before formation of senile plaques. However, persistent Abeta accumulation despite increasing microglial numbers suggests that the ability of microglia to clear Abeta may decrease with age and progression of AD pathology. To determine the effects of aging and Abeta deposition on microglial ability to clear Abeta, we used quantitative PCR to analyze gene expression in freshly isolated adult microglia from 1.5-, 3-, 8-, and 14-month-old transgenic PS1-[[APP]] mice, an established mouse model of AD, and from their nontransgenic littermates. We found that microglia from old PS1-[[APP]] mice, but not from younger mice, have a twofold to fivefold decrease in expression of the Abeta-binding scavenger receptors scavenger receptor A (SRA), [[CD36]], and RAGE (receptor for advanced-glycosylation endproducts), and the Abeta-degrading enzymes insulysin, neprilysin, and [[MMP9]], compared with their littermate controls. In contrast, PS1-[[APP]] microglia had a 2.5-fold increase in the proinflammatory cytokines IL-1beta (interleukin-1beta) and tumor necrosis factor alpha (TNFalpha), suggesting that there is an inverse correlation between cytokine production and Abeta clearance. In support of this possibility, we found that incubation of cultured N9 mouse microglia with TNFalpha decreased the expression of SRA and [[CD36]] and reduced Abeta uptake. Our data indicate that, although early microglial recruitment promotes Abeta clearance and is neuroprotective in AD, as disease progresses, proinflammatory cytokines produced in response to Abeta deposition downregulate genes involved in Abeta clearance and promote Abeta accumulation, therefore contributing to neurodegeneration. Antiinflammatory therapy for AD should take this dichotomous microglial role into consideration.
|mesh-terms=* Aging
* Alzheimer Disease
* Amyloid beta-Peptides
* Animals
* Mice
* Mice, Transgenic
* Microglia
* Signal Transduction

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597474
}}
{{medline-entry
|title=Dietary fructose during the suckling period increases body weight and fatty acid uptake into skeletal muscle in adult rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18483476
|abstract=The suckling period is one potentially "critical" period during which nutritional intake may permanently "program" metabolism to promote increased adult body weight and insulin resistance in later life. This study determined whether fructose introduced during the suckling period altered body weight and induced changes in fatty acid transport leading to insulin resistance in adulthood in rats. Pups were randomly assigned to one of four diets: suckle controls (SCs), rat milk substitute formula (Rat Milk Substitute), fructose-containing formula (Fructose), or galactose-containing formula (Galactose). Starting at weaning, all pups received the same diet; at 8 weeks of age, half of the SC rats began ingesting a diet containing 65% kcal fructose (SC-Fructose). This continued until animals were 12 weeks old and the study ended. At weeks 8, 10, and 11, the Fructose group weighed more than SC and SC-Fructose groups (P < 0.05). At weeks 8 and 10 of age, the Fructose group had significantly higher insulin concentrations vs. rats in the SC-Fructose group. (3)H-Palmitate transport into vesicles from hind limb skeletal muscle was higher in Fructose vs. SC rats (P < 0.05). [[CD36]] expression was increased in the sarcolemma but not in whole tissue homogenates from skeletal muscle from Fructose rats (P < 0.05) suggesting a redistribution of this protein associated with fatty acid uptake across the plasma membrane. This change in subcellular localization of [[CD36]] is associated with insulin resistance in muscle. Consuming fructose during suckling may result in lifelong changes in body weight, insulin secretion, and fatty acid transport involving [[CD36]] in muscle and ultimately promote insulin resistance.
|mesh-terms=* Adipose Tissue
* Aging
* Animals
* Animals, Suckling
* Blood Glucose
* Body Weight
* CD36 Antigens
* Dietary Carbohydrates
* Fatty Acids
* Female
* Fructose
* Insulin
* Leptin
* Liver
* Male
* Models, Animal
* Muscle, Skeletal
* Pregnancy
* Rats
* Rats, Sprague-Dawley
* Triglycerides

|full-text-url=https://sci-hub.do/10.1038/oby.2008.268
}}
{{medline-entry
|title=Complement-associated deposits in the human retina.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18235023
|abstract=The purpose of this study was to investigate complement activation and associated inflammatory mechanisms in normal, aged human retina. Evidence of complement activation and associated mechanisms was assessed in normal human retina (n = 52) using a panel of antibodies directed against membrane attack complex (C5b-9), microglia (CD11b), amyloid precursor protein ([[APP]]), scavenger receptor ([[CD36]]), and a phytolectin (RCA-I). Fifty-two eyes, categorized into two age groups, were used. Nineteen "younger" eyes (<56 years) and 33 "older" eyes (>69 years) with no history of ocular disease were processed between 4 and 22 hours, with a median delay of 14 hours postmortem. Age-dependent expression was evident in C5b-9, [[APP]], CD11b, and RCA-I, but not [[CD36]], immunoreactivity. Immunoreactivity for C5b-9 was robust in Bruch membrane (BM) and the intercapillary pillars of Bruch. Immunoreactivity for [[APP]] was robust in the basal cytoplasm of the retinal pigment epithelium. Immunoreactivity for CD11b was robust on the surface of the retinal pigment epithelial cell, in the choriocapillaris, and in BM. Lectin binding of RCA-I was strong throughout the neuroretina. Robust immunostaining for [[APP]] in older donor eyes suggested that amyloid beta peptides may be one of the triggers of complement activation during the normal aging process. Microglial markers CD11b and RCA-I also increase with age, suggesting a concomitant inflammatory response to C5b-9 deposits in the retinal pigment epithelium, BM, and CC. Immunoreactivity for [[CD36]] was strong in both age groups; the lack of age dependence in this candidate receptor for amyloid beta suggested that complement activation may arise from interactions of amyloid beta with other candidate receptors in normal human retina.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Amyloid beta-Protein Precursor
* Bruch Membrane
* CD11b Antigen
* CD36 Antigens
* Child
* Complement Activation
* Complement Membrane Attack Complex
* Female
* Humans
* Immunoenzyme Techniques
* Male
* Microglia
* Middle Aged
* Pigment Epithelium of Eye
* Plant Lectins
* Retina

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947388
}}
{{medline-entry
|title=Different gene expression patterns in the bone tissue of aging postmenopausal osteoporotic and non-osteoporotic women.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18074071
|abstract=To identify genes that are differently expressed in osteoporotic and non-osteoporotic human bone and to describe the relationships between these genes using multivariate data analysis. Seven bone tissue samples from postmenopausal osteoporotic patients and 10 bone tissue samples from postmenopausal non-osteoporotic women were examined in our study. Messenger RNA was prepared from each sample and reverse transcribed to cDNA. The expression differences of 87 selected genes were analyzed in a Taqman probe-based quantitative real-time RT-PCR system. A Mann-Whitney U-test indicated significant differences in the expression of nine genes (p < or = 0.05). Seven of these nine genes-[[ALPL]], [[COL1A1]], [[MMP2]], [[MMP13]], [[MMP9]], [[PDGFA]], [[NFKB1]]-were significantly downregulated in the bone tissue of osteoporotic women, while [[CD36]] and [[TWIST2]] were significantly upregulated in osteoporotic patients. Principal components analysis was used to evaluate data structure and the relationship between osteoporotic and non-osteoporotic phenotypes based on the multiple mRNA expression profiles of 78 genes. Canonical variates analysis demonstrated further that osteoporotic and non-osteoporotic tissues can be distinguished by expression analysis of genes coding growth factors/non-collagen matrix molecules, and genes belonging to the canonical TGFB pathway. Significant differences observed in gene expression profiles of osteoporotic and non-osteoporotic human bone tissues provide further insight into the pathogenesis of this disease. Characterization of the differences between osteoporotic and non-osteoporotic bones by expression profiling will contribute to the development of diagnostic tools in the future.
|mesh-terms=* Aged
* Aging
* Bone and Bones
* Down-Regulation
* Female
* Gene Expression Profiling
* Gene Expression Regulation
* Genetic Variation
* Humans
* Intercellular Signaling Peptides and Proteins
* Middle Aged
* Multivariate Analysis
* Osteoporosis, Postmenopausal
* Principal Component Analysis
* Proteins
* RNA, Messenger
* Reverse Transcriptase Polymerase Chain Reaction
* Transforming Growth Factor beta
* Up-Regulation

|full-text-url=https://sci-hub.do/10.1007/s00223-007-9092-3
}}
{{medline-entry
|title=[[CD36]] expression contributes to age-induced cardiomyopathy in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17967771
|abstract=Cardiac remodeling and impaired cardiac performance in the elderly significantly increase the risk of developing heart disease. Although vascular abnormalities associated with aging contribute to the age-related decline in cardiac function, myocardium-specific events may also be involved. We show that intramyocardial lipid accumulation, as well as a reduction in both fatty acid and glucose oxidation and a subsequent deterioration in cardiac ATP supply, also occurs in aged mice. Consistent with an energetically compromised heart, hearts from aged mice display depressed myocardial performance and cardiac hypertrophy. Associated with this is a dramatic increase in the fatty acid transport protein [[CD36]] in aged hearts compared with young hearts, which suggests that [[CD36]] is a mediator of these multiple metabolic, functional, and structural alterations in the aged heart. In accordance with this, hearts from aged [[CD36]]-deficient mice have lower levels of intramyocardial lipids, demonstrate improved mitochondria-derived ATP production, have significantly enhanced function compared with aged wild-type mice, and have a blunted hypertrophic response. These findings provide evidence that [[CD36]] mediates an age-induced cardiomyopathy in mice and suggest that inhibition of [[CD36]] may be an approach for the treatment of the detrimental age-related effects on cardiac performance.
|mesh-terms=* Adenosine Triphosphate
* Aging
* Animals
* CD36 Antigens
* Cardiomyopathies
* Energy Metabolism
* Heart
* Heart Function Tests
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Myocardium
* Ventricular Remodeling

|full-text-url=https://sci-hub.do/10.1161/CIRCULATIONAHA.107.712901
}}
{{medline-entry
|title=Lung vitamin E transport processes are affected by both age and environmental oxidants in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17602719
|abstract=Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies the effects of age and two environmental oxidants ozone (O(3)) (0.25 ppm 6 h/day) and cigarette smoke ([[CS]]) (60 mg/m(3) 6 h/day) for 4 days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (p<0.05) and 15% lower (p<0.05) in plasma and lung tissue, respectively, in aged versus young mice, acute environmental exposure to O(3) or [[CS]] at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, [[CD36]], ATP binding cassette 3 ([[ABCA3]]) and [[ABCA1]] and protein levels, determined by Western blots for SRB1, ATTP and [[ABCA1]] were assessed. Aged mouse lung showed a lower levels of ATTP, [[ABCA3]] and SRB1 and a higher level [[CD36]] and [[ABCA1]]. Acute exposure to either O(3) or [[CS]] induced declines in ATTP and SRB1 in both aged and young mice lung. [[CD36]] increased in both young and aged mice lung upon exposure to O(3) and [[CS]]. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types.
|mesh-terms=* ATP Binding Cassette Transporter 1
* ATP-Binding Cassette Transporters
* Aging
* Animals
* Biological Transport
* Blotting, Western
* CD36 Antigens
* Female
* Gene Expression Profiling
* Lipoproteins
* Lung
* Mice
* Mice, Hairless
* Oxidants, Photochemical
* Ozone
* RNA, Messenger
* Reverse Transcriptase Polymerase Chain Reaction
* Scavenger Receptors, Class B
* Smoke
* Tobacco
* Vitamin E

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770005
}}
{{medline-entry
|title=[[CD36]] is a sensor of diacylglycerides.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15690042
|abstract=Toll-like receptor 2 ([[TLR2]]) is required for the recognition of numerous molecular components of bacteria, fungi and protozoa. The breadth of the ligand repertoire seems unusual, even if one considers that [[TLR2]] may form heteromers with TLRs 1 and 6 (ref. 12), and it is likely that additional proteins serve as adapters for [[TLR2]] activation. Here we show that an N-ethyl-N-nitrosourea-induced nonsense mutation of Cd36 (oblivious) causes a recessive immunodeficiency phenotype in which macrophages are insensitive to the R-enantiomer of MALP-2 (a diacylated bacterial lipopeptide) and to lipoteichoic acid. Homozygous mice are hypersusceptible to Staphylococcus aureus infection. Cd36(obl) macrophages readily detect S-MALP-2, PAM(2)CSK(4), PAM(3)CSK(4) and zymosan, revealing that some--but not all--[[TLR2]] ligands are dependent on [[CD36]]. Already known as a receptor for endogenous molecules, [[CD36]] is also a selective and nonredundant sensor of microbial diacylglycerides that signal via the [[TLR2]]/6 heterodimer.
|mesh-terms=* Aging
* Animals
* CD36 Antigens
* Cell Line
* Dimerization
* Ethylnitrosourea
* Gene Deletion
* Glycerides
* Homozygote
* Humans
* Immunologic Deficiency Syndromes
* Lipopeptides
* Membrane Glycoproteins
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Mutagenesis
* Mutation
* Oligopeptides
* Peptidoglycan
* Phenotype
* Receptors, Cell Surface
* Signal Transduction
* Staphylococcal Infections
* Staphylococcus aureus
* Toll-Like Receptor 2
* Toll-Like Receptors
* Tumor Necrosis Factor-alpha
* Zymosan

|full-text-url=https://sci-hub.do/10.1038/nature03253
}}
{{medline-entry
|title=Antennal SNMPs (sensory neuron membrane proteins) of Lepidoptera define a unique family of invertebrate [[CD36]]-like proteins.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/11536197
|abstract=SNMP1-Apol is an antennal-specific protein of the wild silk moth Antheraea polyphemus; the protein is abundantly expressed and localized to the receptor membranes of sex-pheromone specific olfactory sensory neurons (OSNs). SNMP1-Apol is thought to function in odor detection based on its olfactory-specific expression, localization within OSNs, developmental time of expression, and apparent homology to the [[CD36]] family of membrane-bound receptor proteins. In the current study, SNMP1-Apol homologues were identified from the moths Bombyx mori, Heliothis virescens, and Manduca sexta. These species posses antennal mRNAs encoding proteins with amino acid sequence identities ranging from 75-80%; these proteins are collectively designated SNMP1. A second M. sexta SNMP homologue, previously identified and partially sequenced [Robertson et al.: Insect Mol Biol 8:501-518, 1999] was fully sequenced and characterized. The encoded protein shares only 26-27% sequence identity with the SNMP1 proteins, and is thus designated SNMP2-Msex. The SNMP sequences were used to identify 14 and four possible homologues in Drosophila melanogaster and Caenorhabditis elegans genome databases, respectively; thus, greatly expanding [[CD36]] family membership among the invertebrate lineages. Despite their sequence difference, SNMP1-Msex and SNMP2-Msex expression is localized to OSNs and occurs simultaneously with the onset of olfactory function. These findings suggest that SNMPs play a central role in odor detection in insects, and that the [[CD36]] gene family is widely represented among animal phyla. The SNMPs are the only identified neuronal members of the [[CD36]] family, and as such expand the activities of this gene family into roles influencing brain function and behavioral action.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Bombyx
* CD36 Antigens
* Insect Proteins
* Lepidoptera
* Male
* Manduca
* Membrane Proteins
* Molecular Sequence Data
* Nerve Tissue Proteins
* Sense Organs
* Tissue Distribution

|full-text-url=https://sci-hub.do/10.1002/neu.1065
}}
{{medline-entry
|title=Putative membrane fatty acid translocase and cytoplasmic fatty acid-binding protein are co-expressed in rat heart and skeletal muscles.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/7864868
|abstract=A membrane protein (FAT) homologous to [[CD36]] has recently been implicated in the binding and transport of long-chain fatty acids (FA). Expression of this protein in rat heart, skeletal muscles and in isolated cardiac cells was studied. Changes in expression during development of the heart were also examined. Expression of FAT was compared to that of the cytoplasmic fatty acid-binding protein (H-FABP) to determine whether coexpression, indicative of related biological functions, could be demonstrated. FAT and H-FABP mRNAs showed a similar muscle tissue distribution and similar cellular localization in the heart. During development, heart mRNA levels for both proteins were upregulated in the same way. In conclusion, expression of FAT and H-FABP in muscle tissues and cell-types with high FA metabolism and the upregulation of mRNA levels associated with heart development, when FA utilization increases, support the suggested role of both proteins in FA metabolism.
|mesh-terms=* Adipose Tissue
* Aging
* Animals
* Animals, Newborn
* Blotting, Northern
* Carrier Proteins
* Cell Membrane
* Cells, Cultured
* Cytoplasm
* Enzyme-Linked Immunosorbent Assay
* Fatty Acid-Binding Protein 7
* Fatty Acid-Binding Proteins
* Fatty Acids
* Gene Expression
* Heart
* Liver
* Muscle, Skeletal
* Myocardium
* Neoplasm Proteins
* Nerve Tissue Proteins
* RNA, Messenger
* Rats
* Rats, Inbred WKY

|full-text-url=https://sci-hub.do/10.1006/bbrc.1995.1250
}}