LEP and obesity due to melanocortin 4 receptor deficiency: In 3 T3-L1 preadipocytes, demethylation did not increase leptin gene expression, and the diet-induced up-regulation of leptin, Mest/Peg1, and sFRP5 gene expression in white adipose tissue (WAT) during the development of obesity in mice is not mediated directly by changes in DNA methylation [44].