In summary, our results clearly indicate that skeletal muscle-specific disruption of JNK-1 fails to affect body composition and energy homeostasis in lean and obese mice indicating that JNK-1-dependent signaling in other organs than skeletal muscle accounts for the protective effect of JNK-1 deficiency against the development of diet-induced obesity. This evidence concerns the gene MAPK8 and obesity due to melanocortin 4 receptor deficiency.