Together, these data suggest that the deregulated expression of Ahsg, Angptl4, Fetub, Fgf21 and Lect2 may be highly relevant in mediating muscle insulin hypersensitivity and decrease adiposity in LPTENKO mice, therefore highlighting these hepatokines as important modulators of insulin sensitivity, steatosis and obesity in both rodents and humans. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.