Consistently, AT-Sdc4 KO mice exhibit elevated HSL-mediated lipolysis and FFA oxidation while treatment with recombinant Sdc4 (RbSdc4) impairs lipolysis in adipocytes by decreasing HSL activity and FFA release indicating that the adipocyte-derived shed Sdc4 of HFD-fed mice acts in an autocrine manner to disrupt lipid metabolism, thereby aggravating the development of obesity. This evidence concerns the gene SDC4 and obesity due to melanocortin 4 receptor deficiency.