In vitro and in vivo experiments suggested that the Klf9 overexpression caused macrophage deactivation and reduced the secretion of factors including IL-6, prostaglandin E2 (PGE2) and IL-10, thereby inhibiting thermogenesis and increasing lipid accumulation in adipocytes by inhibiting STAT3 signaling, which eventually led to obesity. This evidence concerns the gene KLF9 and obesity due to melanocortin 4 receptor deficiency.