Role of visceral adipose tissue in aging

Background

Visceral fat (VF) accretion is a hallmark of aging in humans. Epidemiologic studies have implicated abdominal obesity as a major risk factor for insulin resistance, type 2 diabetes, cardiovascular disease, metabolic syndrome and death.

Methods

Studies utilizing novel rodent models of visceral obesity and surgical strategies in humans have been undertaken to determine if subcutaneous (SC) abdominal or VF are causally linked to age-related diseases.

Results

Specific depletion or expansion of the VF depot using genetic or surgical tools in rodents has been shown to have direct effects on disease risk. In contrast, surgically removing large quantities of SC fat does not consistently improve metabolic parameters in humans or rodents, while benefits were observed with SC fat expansion in mice, suggesting that SC fat accrual is not an important contributor to metabolic decline. There is also compelling evidence in humans that abdominal obesity is a stronger risk factor for mortality risk than general obesity. Likewise, we have shown that surgical removal of VF improves mean and maximum lifespan in rats, providing the first causal evidence that VF depletion may be an important underlying cause of improved lifespan with caloric restriction.

General significance

This review provides both corollary and causal evidence for the importance of accounting for body fat distribution, and specifically VF, when assessing disease and mortality risk. Given the hazards of VF accumulation on health, treatment strategies aimed at selectively depleting VF should be considered as a viable tool to effectively reduce disease risk in humans.     

视黄酸X受体α促进猪前体脂肪细胞分化

采用细胞转染、油红O染色、油红O染色提取法、GPDH活性测定、semi-qRT-PCR等方法研究了视黄酸X受体α (retinoic acid X receptor α, RXRα)在猪原代前体脂肪细胞分化中的作用及其机理.结果表明,转染pRXRα-EGFP促进了猪前体脂肪细胞RXRα 的表达,脂肪细胞分化能力随之增强, 脂肪细胞GPDH活性、分化转录因子PPARγ和C/EBPαmRNA表达水平均显著升高(P<0.05). 结果提示,RXRα可能通过调控过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptor-γ, PPARγ)和CAAT/增强子结合蛋白家族（CCAAT/enhancer binding proteins, C/EBP）C/EBPα 基因表达变化促进猪前体脂肪细胞分化.     

Association of monocyte chemoattractant protein-1 with adipocyte number, insulin resistance and liver function markers

Background  Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory chemokine known to induce adipocyte dedifferentiation and insulin resistance. Inflammation, insulin resistance, and obesity have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD).
Methods  Fasting plasma from 43 baboons were assayed for MCP-1, insulin, glucose, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Adipocyte number and volume were measured via biopsies of omental adipose tissue. The homeostatic model assessment method (HOMA) was used to estimate systemic insulin resistance.
Results  Sex and age adjusted correlations were significant for MCP-1 with adipocyte number (r = −0.42; P  = 0.01), adipocyte volume (r = 0.38; P  = 0.02), HOMA (r = 0.45; P  = 0.004), ALT (r = 0.46; P  = 0.03) and AST (r = 0.45; P  = 0.03).
Conclusions  These results suggest that MCP-1 is related with adipocyte dedifferentiation and systemic insulin resistance, thereby potentially contributing to the development of NAFLD.     

Association of A-FABP gene polymorphism in intron 1 with meat quality traits in Junmu No. 1 white swine

This study was designed to investigate the single nucleotide polymorphism (SNP) in intron 1 of the gene A-FABP in 127 Junmu No. 1 white swine using PCR-SSCP. The association between the polymorphism and meat quality traits was also studied. The cloning and sequencing results indicated that the polymorphism of intron 1 was due to a point mutation in position 3481 bp of A-FABP, giving 3 genotypes (CC, CD and DD). Association analysis indicated that the polymorphism had a significant effect on marbling (P < 0.05). Genotype DD had higher marbling than CD and CC, but the difference between CD and CC was no significant. Polymorphism had a highly significant effect on intramuscular fat (IMF) content (P < 0.01). DD was higher than CD, which was higher than CC. No significant conclusions can be drawn regarding other traits. Immunoblot analysis of A-FABP levels was carried out on 3 different genotype individuals. Expression was markedly reduced in DD compared with genotype CC. Thus A-FABP may be a candidate gene or a quantitative trait locus-linked gene associated with meat quality traits.     

Zebrafish obesogenic test: a tool for screening molecules that target adiposity

Dietary and xenobiotic compounds may alter endocrine signaling and lipid homeostasis, thus inducing obesity. We describe a short-term assay method, the zebrafish obesogenic (ZO) test, for examining the effects of diet, drugs, and environmental contaminants, singly or in combination, on white adipose tissue (WAT) dynamics in live larvae. The ZO test is an intermediate step in obesity research, between in vitro and rodent assays, and may be also used to study the effect of environmental toxicants on the adiposity of aquatic species. The procedure, using Nile Red (NR) fluorescent probe to reveal adipocyte lipid droplets, is suitable for pharmaceutical or toxicological screening. Larvae treated at an environmentally-relevant concentration of tributyltin chloride (TBT), an environmental obesogen, exhibited a remarkable increase in adiposity, irrespective of the lipid composition of the background diet. Exogenous compounds, e.g., rosiglitazone or TBT, known to increase adiposity in the fasting state, were classified as obesogenic. Anti-obesogenic compounds favored a decrease in adiposity in the fasting state. The ZO test, using adipocyte lipid droplet size and adiposity as its endpoints, is a whole-organism alternative testing assay for obesogenic and anti-obesogenic compounds and mixtures and provides relevant information for environmental and human risk assessments.