It is possible that the initial weight gain in nutritional phase 2a results from impaired central and hepatic insulin signaling driving increased peripheral insulin secretion and a general increase in lean mass, while the onset of obesity in phase 2b is driven primarily by increased total fat mass and leptin due to elevated insulin signaling in adipose tissue.22, 23. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.