Редактирование: FABP3

Fatty acid-binding protein, heart (Fatty acid-binding protein 3) (Heart-type fatty acid-binding protein) (H-FABP) (Mammary-derived growth inhibitor) (MDGI) (Muscle fatty acid-binding protein) (M-FABP) [FABP11] [MDGI]

==Publications==

{{medline-entry
|title=[[FABP3]]-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33168829
|abstract=Sarcopenia is characterized by decreased skeletal muscle mass and function with age. Aged muscles have altered lipid compositions; however, the role and regulation of lipids are unknown. Here we report that [[FABP3]] is upregulated in aged skeletal muscles, disrupting homeostasis via lipid remodeling. Lipidomic analyses reveal that [[FABP3]] overexpression in young muscles alters the membrane lipid composition to that of aged muscle by decreasing polyunsaturated phospholipid acyl chains, while increasing sphingomyelin and lysophosphatidylcholine. [[FABP3]]-dependent membrane lipid remodeling causes ER stress via the PERK-eIF2α pathway and inhibits protein synthesis, limiting muscle recovery after immobilization. [[FABP3]] knockdown induces a young-like lipid composition in aged muscles, reduces ER stress, and improves protein synthesis and muscle recovery. Further, [[FABP3]] reduces membrane fluidity and knockdown increases fluidity in vitro, potentially causing ER stress. Therefore, [[FABP3]] drives membrane lipid composition-mediated ER stress to regulate muscle homeostasis during aging and is a valuable target for sarcopenia.
|mesh-terms=* Aging
* Animals
* Cell Line
* Endoplasmic Reticulum Stress
* Eukaryotic Initiation Factor-2
* Fatty Acid Binding Protein 3
* Female
* Gene Knockdown Techniques
* Lipidomics
* Membrane Fluidity
* Membrane Lipids
* Mice, Inbred C57BL
* Mice, Knockout
* Muscle, Skeletal
* Myoblasts
* Phospholipids
* Protein-Serine-Threonine Kinases
* Sarcopenia
* Up-Regulation

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653047
}}
{{medline-entry
|title=Autophagy receptor [[OPTN]] (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing [[FABP3]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33143524
|abstract=Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. [[OPTN]] (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified [i]Optn[/i] as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as [i]optn [/i]   mice. Importantly, restoring [i]Optn[/i] by transplanting wild-type MSCs to [i]optn [/i]   mice or infecting [i]optn [/i]   mice with [i]Optn[/i]-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of [i]Optn [/i] failed to reestablish a bone-fat balance. We further identified [[FABP3]] (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of [[OPTN]]. [[FABP3]] promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of [[FABP3]] alleviated bone loss in [i]optn [/i]   mice and aged mice. Our study revealed that reduced [[OPTN]] expression during aging might lead to OP due to a lack of [[FABP3]] degradation via selective autophagy. [[FABP3]] accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating [[OPTN]] or inhibiting [[FABP3]] would open a new avenue to treat senile OP.   ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; [[NBR1]]: [[NBR1]], autophagy cargo receptor; OP: osteoporosis; [[OPTN]]: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-[[GLB1]]: senescence-associated (SA)-[[GLB1]] (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; μCT: micro computed tomography.

|keywords=* Adipogenesis
* autophagy
* bone metabolism
* fabp3
* mesenchymal stem cell
* optineurin
* osteogenesis
* osteoporosis
* senescence
|full-text-url=https://sci-hub.do/10.1080/15548627.2020.1839286
}}
{{medline-entry
|title=Myokines as biomarkers of frailty and cardiovascular disease risk in females.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32017952
|abstract=Frailty is a risk factor for cardiovascular disease (CVD). Biomarkers have the potential to detect the early stages of frailty, such as pre-frailty. Myokines may act as biomarkers of frailty-related disease progression, as a decline in muscle health is a hallmark of the frailty phenotype. This study is a secondary analysis of 104 females 55 years of age or older with no previous history of CVD. Differences in systemic myokine concentrations based on frailty status and CVD risk profile were examined using a case-control design. Propensity matching identified two sets of 26 pairs with pre-frailty as the exposure variable in low or elevated CVD risk groups for a total 104 female participants. Frailty was assessed using the Fried Criteria (FC) and CVD risk was assessed using the Framingham Risk Score (FRS). Factorial ANOVA compared the main effects of frailty, CVD risk, and their interaction on the concentrations of 15 myokines. Differences were found when comparing elevated CVD risk status with low for the concentrations of [[EPO]] (384.76 ± 1046.07 vs. 206.63 ± 284.61 pg/mL, p = .001), [[FABP3]] (2772.61 ± 3297.86 vs. 1693.31 ± 1019.34 pg/mL, p = .017), [[FGF21]] (193.17 ± 521.09 vs. 70.18 ± 139.51 pg/mL, p = .010), IL-6 (1.73 ± 4.97 vs. 0.52 ± 0.89 pg/mL, p = .023), and IL-15 (2.62 ± 10.56 vs. 0.92 ± 1.25 pg/mL, p = .022). Pre-frail females had lower concentrations of fractalkine compared to robust (27.04 ± 20.60 vs. 103.62 ± 315.45 pg/mL, p = .004). Interaction effects between frailty status and CVD risk for [[FGF21]] and [[OSM]] were identified. In elevated CVD risk, pre-frail females, concentrations of [[FGF21]] and [[OSM]] were lower than that of elevated CVD risk, robust females (69.10 ± 62.86 vs. 317.24 ± 719.69, p = .011; 1.73 ± 2.32 vs. 24.43 ± 69.21, p = .018, respectively). These data identified specific biomarkers of CVD risk and biomarkers of frailty that are exacerbated with CVD risk.

|keywords=* Aging
* Biomarkers
* Cardiovascular disease
* Females
* Frailty
* Myokines
|full-text-url=https://sci-hub.do/10.1016/j.exger.2020.110859
}}