ADIPOQ
Adiponectin precursor (30 kDa adipocyte complement-related protein) (Adipocyte complement-related 30 kDa protein) (ACRP30) (Adipocyte, C1q and collagen domain-containing protein) (Adipose most abundant gene transcript 1 protein) (apM-1) (Gelatin-binding protein) [ACDC] [ACRP30] [APM1] [GBP28]
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In the present study, we aimed to investigate the impact of permanent cystathionine-β-Synthase (CBS) gene knockdown in human telomerase reverse transcriptase (hTERT) immortalized human adipose-derived mesenchymal stem cells (ASC52telo) and in their capacity to differentiate into adipocytes. CBS gene KD in ASC52telo cells led to increased cellular inflammation (IL6, CXCL8, TNF) and oxidative stress markers (increased intracellular reactive oxygen species and decreased reduced glutathione levels) in parallel to decreased H S production and rejuvenation (LC3 and SIRT1)-related gene expression. In addition, CBS gene KD in ASC52telo cells resulted in altered mitochondrial respiratory function, characterised by decreased basal respiration (specifically proton leak) and spare respiratory capacity, without significant effects on cell viability and proliferation. In this context, shCBS-ASC52telo cells displayed enhanced adipogenic (FABP4, ADIPOQ, SLC2A4, CEBPA, PPARG)-, lipogenic (FASN, DGAT1)- and adipocyte (LEP, LBP)-related gene expression markers, decreased expression of proinflammatory cytokines, and increased intracellular lipid accumulation during adipocyte differentiation compared to control ASC52telo cells. Otherwise, the increased adipogenic potential of shCBS-ASC52telo cells was detrimental to the ability to differentiate into osteogenic linage. In conclusion, this study demonstrated that permanent CBS gene KD in ASC52telo cells promotes a cellular senescence phenotype with a very increased adipogenic potential, promoting a non-physiological enhanced adipocyte differentiation with excessive lipid storage.
Keywords
- Cellular senescence
- Cystathionine β-synthase
- Human adipose-derived mesenchymal stem cells
- Inflammation
- Oxidative stress and adipogenesis
Sarcopenia, the aging-related deterioration of skeletal muscle, is a disease that is directly associated with quality of life. Given the trend of an increasing aging population worldwide, the prevention of aging-related diseases such as sarcopenia has become ever more important and urgent. To identify potential therapeutic targets for this disease. we used a bioinformatics approach of combining cDNA microarray analysis and protein-protein interaction prediction. We found 673 significant differentially expressed genes (128 upregulated and 545 downregulated) in sarcopenia patients of over 60 years of age. Most of the upregulated genes were involved in metabolic processes such as the PPAR signaling pathway. In particular, FABP4, PLIN1, and ADIPOQ were related to fatty acid and lipid metabolism. Some of the downregulated genes were located in the mitochondrial matrix. Additionally, through the protein interaction network analysis, we found two key molecules (MAP1LC3B and HSP90AB1) that were associated with autophagy. These results suggest that mitochondrial dysfunction and lipid metabolism are associated with sarcopenia.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- DNA, Mitochondrial
- Female
- Humans
- Male
- Microarray Analysis
- Middle Aged
- Muscle Strength
- Muscle, Skeletal
- Sarcopenia
Keywords
- Alzheimer’s disease
- aging
- microarray
- protein–protein interaction
Age-related hearing impairment (ARHI) is a complex neurodegenerative disorder caused by a combination of environmental and genetic factors. We have reported previously that obesity increases the risk for ARHI, and that plasma levels of adiponectin are associated with ARHI. In the present study, we further explored the role of adiponectin in the pathophysiology of ARHI by investigating the genotypes of ADIPOQ and ADIPOR1, the genes of adiponectin and its type 1 receptor, respectively. A total of 1682 volunteers were enrolled, and their audiological phenotypes were determined according to the z scores converted from their original frequency-specific hearing thresholds. A total of 9 tag-single nucleotide polymorphisms (tagSNPs) in ADIPOQ and 4 tagSNPs in ADIPOR1 were genotyped, and the genotypes were correlated to the audiological phenotypes under the assumption of various inheritance models. Significant associations were identified between certain ADIPOQ tagSNPs and z scores under dominant, codominant, or additive models, whereas no association was identified between ADIPOR1 tagSNPs and z scores. The associations between ADIPOQ tagSNPs and z scores appear to exist only in subjects with specific ADIPOR1 genotypes, indicating an interaction between adiponectin and AdipoR1. Measurement of plasma adiponectin in 736 subjects revealed that ADIPOQ genotypes might exert their effects on hearing levels via modulation of plasma adiponectin levels. Subsequently, we confirmed the expression of AdipoR1 in the inner ear of mice, and demonstrated antiapoptotic effects of adiponectin in cochlear explant cultures. These results provide insights into the physiological function and potential clinical implications of adiponectin against ARHI.
MeSH Terms
- Adiponectin
- Adult
- Aged
- Aged, 80 and over
- Aging
- Animals
- Apoptosis
- Cells, Cultured
- Cochlea
- Ear, Inner
- Epistasis, Genetic
- Female
- Genetic Association Studies
- Genotype
- Hearing Loss
- Humans
- Male
- Mice
- Middle Aged
- Polymorphism, Single Nucleotide
- Receptors, Adiponectin
Keywords
- ADIPOR1
- Adiponectin
- Age-related hearing impairment
Adiponectin demonstrates a protective role against the development of obesity, type 2 diabetes mellitus, and cardiovascular disease. The -11377C 〉 G, -11391G 〉 A, and -11426A 〉 G promoter polymorphisms of ADIPOQ gene influence the level of circulating adiponectin. We examined the level of total and high molecular weight (HMW) adiponectin in centenarians and associated it with biochemical parameters. We checked if the expression and concentration-modifying polymorphisms of ADIPOQ are associated with extreme longevity. Total and HMW adiponectin were examined using ELISA in 40 female centenarians. The frequencies of the ADIPOQ polymorphisms were tested by restriction fragment length polymorphism in 148 centenarians, 414 young controls, in 207 myocardial infarction patients, and in 190 type 2 diabetes mellitus patients. The mean concentration of total adiponectin in centenarians was 13.19 ± 1.37 mg/mL and of HMW adiponectin it was 9.17 ± 1.15 mg/mL. They were positively correlated with HDL (r = 0.4696, p = 0.0025 and r = 0.3912, p = 0.015, respectively), and negatively with BMI (r = -0.3702, p = 0.034 and r = -0.3963, p = 0.025) and triglycerides (r = -0.346, p = 0.028 and r = -0.3227, p = 0.045). A very rare AA genotype of the -11391G 〉 A polymorphism was significantly more common in centenarians than in young controls (p = 0.026) and, while compared to the GG genotype, it was associated with a 2.4-fold higher mean concentration of total adiponectin (26.53 ± 13.29 mg/ mL v. 10.97 ± 4.28 mg/mL) and with an almost 3-fold higher mean HMW adiponectin (20.65 ± 12.72 mg/mL v. 7.36 ± 3.35 mg/mL). Serum adiponectin concentration in female centenarians is associated with biochemical parameters that are favourable for cardiovascular risk. We suggest that adiponectin might be of importance for extreme longevity.
MeSH Terms
- Adiponectin
- Aged, 80 and over
- Body Mass Index
- Case-Control Studies
- Enzyme-Linked Immunosorbent Assay
- Female
- Genotype
- Humans
- Longevity
- Molecular Weight
- Polymorphism, Restriction Fragment Length
- Polymorphism, Single Nucleotide
- Real-Time Polymerase Chain Reaction
- Risk Factors
Adipokines are important for regulation body metabolism and immune response. Many studies have shown that variants in adipokines genes play a role in age-associated diseases. In this study, we investigated the contribution of rs266729 (-11377G/C), rs2241766 ( 45T/G), and rs1501299 ( 276 G/T) SNPs of adiponectin gene (ADIPQO) and rs7799039 (-2548C/A) SNP of leptin (LEP) gene to human longevity phenotype in Jordanian population. Polymorphisms were genotyped in 110 randomly selected elderly subjects (>85 years old) with mean age of 90.2 years, and 120 young control subjects (range from 20 to 50 years) with mean age of 32.0 years. No significant differences were detected in the genotype and allele frequencies of examined gene variants between the two groups (p > 0.05). However, when gender was considered, genotypes and alleles frequencies of rs1501299 SNP in ADIPOQ gene and rs7799039 in LEP gene were significantly associated with longevity in men (p < 0.02) but not in women (p > 0.05). Thus, ADIPOQ and LEP genes polymorphisms might play a gender-specific role in the pathway to men's longevity.
MeSH Terms
- Adiponectin
- Adult
- Aged, 80 and over
- Female
- Gene Frequency
- Genetic Association Studies
- Humans
- Jordan
- Leptin
- Longevity
- Male
- Middle Aged
- Polymorphism, Genetic
- Polymorphism, Single Nucleotide
- Sex Factors
- Young Adult