It is shown that the expression of both AdipoR1/R2 is significantly decreased in the adipose tissue and muscle of insulin-resistant ob/ob mice, probably due in part to obesity-associated hyperinsulinemia through FoxO (53), with adiponectin-induced AMPK activation also shown to be impaired in the skeletal muscle of these mice, suggesting that adiponectin resistance is present in ob/ob mice, clearly due to decreases in the expression of AdipoR1/R2. The gene discussed is ADIPOR1; the disease is obesity due to melanocortin 4 receptor deficiency.