Rat insulin promoter (RIP25Mgn)-Cre;Lepr mice display hyperglycemia and reduced insulin secretion, but they also have high adiposity due to RIP-CreMgn activity in the brain (19, 20); the disrupted glucose homeostasis is likely a secondary effect to obesity associated with loss of Lepr in the hypothalamus. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.