Methylation of Hypothalamic Tsc1-mTOR Signaling in Regulation of Obesity and Obesity Resistance

The Tsc1-mTOR signaling pathway is often related to obesity, and epigenetic modification may lead to expression changes of obesity-related gene. Therefore, we aim to investigate the methylation of the Tsc1-mTOR signaling pathway in regulation of obesity susceptibility. Wistar rats were fed a normal diet or a high-fat diet to develop animal models. Protein and mRNA expression levels of Tsc1-mTOR signaling in the hypothalamus were determined by Western blot and quantitative real-time PCR. Methylation of Tsc1 gene promoter was detected by bisulfite genomic sequence. Both mRNA and protein expression levels of Tsc1 in DIO group hypothalamus were lower; mTOR and its downstream targets S6K1, 4EBP1, and S6 protein expression levels were higher than those of the DIO-R group and the chow group. The Tsc1 gene promoter methylation rate in the hypothalamus was 92.05 ± 3.07 % in the DIO group, 87.27 ± 1.91 % in the DIO-R group, and 88.18 % ± 3.20 % in the chow group, respectively, with significantly higher levels in the DIO group. Both the expression levels of Tsc1 gene promoter methylation and Tsc1-mTOR signaling pathway in the hypothalamus of DIO rats and DIO-R rats are different. These findings may shed light on the potential mechanism for the differentiation of obesity susceptibility.

Relationship of FTO gene variations with NAFLD risk in Chinese men

BackgroundFat mass and obesity-associated (FTO) gene is an obesity susceptibility gene and its relationship with the nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aims to investigate the relationships of FTO gene variations with NAFLD risk in a Chinese male population.MethodsA 1:2 matched case–control study was performed on 275 cases of NAFLD and 550 controls matched for age. Nine of the FTO gene single nucleotide polymorphisms (SNPs) were genotyped.ResultsLogistic regression analysis found that FTO rs1477196 was significantly associated with the susceptibility to NAFLD in recessive genetic models [unadjusted odds ratio (OR) = 2.52, 95% confidence interval (CI): 1.22–5.19, P = 0.012] and the relativity weakened after further adjustment for body mass index (BMI), uric acid, metabolic syndrome, smoking, and drinking (adjusted OR = 2.18, 95% CI: 0.96–4.99, P = 0.06). In the obese group, the AA + AG genotypes of rs1121980 and rs9940128 were associated with a decreased risk of NAFLD, when compared with the GG genotype, respectively (rs1121980: adjusted OR = 0.62, 95% CI = 0.39–0.99, P = 0.044; rs9940128: adjusted OR = 0.61, 95% CI = 0.38–0.97, P = 0.038). Furthermore, rs1477196 was associated with the severity of NAFLD (OR = 2.95, 95% CI = 1.09–7.94, P = 0.034).ConclusionsOur results demonstrated that the FTO gene was related to the presence and severity of NAFLD in a Chinese male population, and the relationships of the tested SNPs with NAFLD are most probably mediated by BMI.

Environmental Obesogens and Their Impact on Susceptibility to Obesity: New Mechanisms and Chemicals

The incidence of obesity has reached an all-time high, and this increase is observed worldwide. There is a growing need to understand all the factors that contribute to obesity to effectively treat and prevent it and associated comorbidities. The obesogen hypothesis proposes that there are chemicals in our environment termed obesogens that can affect individual susceptibility to obesity and thus help explain the recent large increases in obesity. This review discusses current advances in our understanding of how obesogens act to affect health and obesity susceptibility. Newly discovered obesogens and potential obesogens are discussed, together with future directions for research that may help to reduce the impact of these pervasive chemicals.