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. Here, FETUB is linked to obesity due to melanocortin 4 receptor deficiency.