IRS1 and obesity due to melanocortin 4 receptor deficiency: As presented in Fig. 2A, insulin-stimulated IRS1 (Tyr632) phosphorylation increased with resveratrol treatment in lean subjects but not in subjects with severe obesity (1.9 ± 0.2 vs. 1.3 ± 0.1 fold increase over the noninsulin, nonresveratrol-treated condition, for lean vs. severely obese, respectively, P < 0.05).