Although weight loss achieved by caloric restriction and/or exercise, lowers insulin resistance (Amati et al., 2009; Menshikova et al., 2005), and increases the action of insulin to suppress fatty acid oxidation to a similar degree in individuals with obesity (Corpeleijn et al., 2008), the role of caloric restriction on mitochondrial physiology is somewhat unclear. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.