Mice fed with a high-fat diet (HFD) develop obesity, hyperinsulinemia, and hyperglycemia and exhibit elevation of hepatic glucose production, demonstrated by increased expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and by hyperinsulinemic-euglycemic clamp studies [5,6]. Here, G6PC1 is linked to obesity due to melanocortin 4 receptor deficiency.