Abstract
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.
Highlights
Obesity is known to be the imbalance of energy intake and consumption caused by genetic and environmental factors
After 14 weeks of feeding, in the HFD group, 8 rats were considered as the diet-induced obesity (DIO) group and 6 rats were considered as the diet-induced obesity resistance (DIO-R) group
We found that compared with DIOR rats, the expression levels of Tuberous sclerosis syndrome 1 (Tsc1) mRNA and protein in DIO rat hypothalamus showed a downward trend, and the expression levels of mammalian target of rapamycin (mTOR) and its downstream targets S6 protein kinase 1 (S6K1), 4EBP1, and S6 increased
Summary
Obesity is known to be the imbalance of energy intake and consumption caused by genetic and environmental factors. In 2016, more than 1.9 billion adults were overweight; of these, over 650 million were obese, and over 340 million children and adolescents aged 5–19 were overweight or obese. Effective weight control can improve obesity complications and coexistence diseases, reducing the total cause of mortality [2]. A more comprehensive way to reveal the pathogenesis of obesity and to find safe and effective therapeutic targets has become an urgent medical and social problem for people with obesity. Not all people or rodents will be obese under the same genetic and environmental effects; human and animals have different susceptibility to obesity, and there are obesity and obesity resistance [3]. We will study the pathogenesis of obesity from the perspective of obesity susceptibility
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