While animal models of obesity have demonstrated that regular aerobic exercise with swimming can attenuate insulin resistance through the regulation of ASK-1-mediated insulin signaling [126], animal models of NAFLD have not examined changes in ASK-1 signaling directly and have demonstrated inconsistent results with multiple studies showing both increased and decreased ERS in the liver [127]. Here, MAP3K5 is linked to obesity due to melanocortin 4 receptor deficiency.