In mice, Sema3G activates the phosphatidylinositol-3 kinase (PI3K)–Akt–glycogen synthase kinase 3 (GSK3) and AMP-activated protein kinase (AMPK)–sterol regulatory element binding protein-1c (SREBP-1c) signaling pathways in adipose tissues and the liver, respectively, leading to obesity and insulin resistance. The gene discussed is SEMA3G; the disease is obesity due to melanocortin 4 receptor deficiency.