LEP and obesity due to melanocortin 4 receptor deficiency: Indeed, we recently studied two experimental murine obesity models, viz., diet-induced obesity wherein in high-fat-feeding increases hepatic ceramide levels and thereby causes excessive activation of hepatic aPKC [13], and hereditarily obese ob/ob mice [18], wherein, the congenital absence of leptin leads to (a) increases in appetite and food intake, and (b) decreases in energy expenditure.