In this study, we detected the expression levels of Tsc1 gene promoter methylation and Tsc1-mTOR signaling pathway in the hypothalamus between diet-induced obesity (DIO) rats and diet-induced obesity resistance (DIO-R) rats to investigate the potential regulation mechanism for the differentiation of obesity susceptibility. This evidence concerns the gene TSC1 and obesity due to melanocortin 4 receptor deficiency.