Expression Of Obesity-Related Gene In Subcutaneous And Omental Adipose Tissue In Children And Depot-Specific Regulation On Obesity-Related Gene

The prevalence of overweight and obesity has become a major global public health concern also in children. A significant amount of investigation has been shown the link between childhood and adult obesity and the potential long-term health consequences of childhood obesity. There is increasing evidence to support the view that overweight and obesity during childhood and adolescence is significantly associated with insulin resistance, dyslipidemia and elevated blood pressure in young adulthood. The mechanisms that account for the increased risk associated with obesity at these ages remain unclear.Obesity, notably central (visceral) obesity is closely linked to insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cardiovascular disease and premature death. The detailed molecular basis for this association is subject to intense research.. It is now widely accepted that white adipose tissue (WAT) produced a variety of bioactive peptides, including leptin, tumour necrosis factor a (TNFa), interleukin-6 (IL-6) adipsin and acylation-stimulating protein (ASP), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin etc., and also activate steroid hormones (eg. Convert cortisone to cortisol). They have been implicated in the development of obesity and/or insulin resistance and type 2 diabetes. In animal model and adults, genes coding for some of these proteins maybe differently expressed in subcutaneous (SC) and omental (OM) adipose tissue, thereby playing a key role in the metabolic disorders linked to visceral obesity.The objective of this work was to investigate (1) The expression levels of obesity related gene in paired samples of SC and OM adipose tissue during childhood (2) The possible mechanism of regulation in depot-specific gene expression.In the first study, we measured mRNA levels of 11-hydroxysteroid dehydrogenate type 1(11 HSD1), leptin, TNFa, resistin, adiponectin and PPARy in subcutaneous (SC) and omental (OM) adipose tissue from 54 children (0.17-16 years of age, body mass index, BMI 13.1-30.5 kg/m, 43 normal weght, 13 overweight) and 16 adults (28-72 years old, BMI 19-46 kg/m), we also compared cellular inhibitor of apoptosis protein 2 (cIAP2) expression level in SC and OM adipose tissue from 23 patients (12 children: 13.6-21 .2 kg/m; 11adults: BMI 18.0-29.9 kg/m).and cIAP2 mRNA level was higher in OM adipose tissue compared to SC adipose tissue. In contrast, the leptin mRNA levels were significantly higher in SC compared to OM adipose tissue. Adiponectin mRNA level was significantly lower in OM in the group of overweight children, whereas there was no such site difference in the group of normal weight children. Correlation analysis indicated that 1 IpHSDl and leptin in SC were positively associated with BMI, whereas 11HSD1 in OMincreased with age. Adiponectin mRNA levels in adipose tissue were positively associated to PPAR mRNA in both children and adults.Our results demonstrated that depot-specific expression in mRNA levels of 11HSD1, leptin and cIAP2 were present already in childhood. The elevated level of 11HSD1 mRNA in OM with age may reflect a causal role in visceral fat accumulation during childhood. Increasing 11HSDland leptin mRNA in SC with increasing BMI may suggest that the risk of the metabolic consequences of obesity occur relative early in life. Decreased adiponectin expression in OM relative to SC in overweight children, suggests that susceptibility to develop insulin resistance is present already in childhood and after relatively short duration of overweight. This may explain, at least partly, the increasing problem with insulin resistance and type 2 diabetes in obese children. The close association between adiponectin and PPARy expression support the suggestion that PPAR is involved in adiponectin gene regulation.In the second study, the effects of dexamethsone (DEX) and PPAR agonist (Triglitazone, TGZ) on genes expression in adipose tissue fragments was investigated in vitro studies. SC and OM adipose tissue from adults were incuba...