MTOR and obesity due to melanocortin 4 receptor deficiency: In agreement, the activation of mTOR pathway is elevated in the liver and in the skeletal muscle of insulin-resistant obese rats maintained on a high-fat diet, whereas absence of a downstream mTOR target, the ribosomal S6 kinase (S6K), protects against diet-induced obesity and enhances insulin sensitivity in mice [183, 328].