Elevated plasma free fatty acids (FFAs), as found in obesity, induce hepatic insulin resistance.1, 2, 3 Prolonged exposure of hepatocytes to FFAs activates p38 mitogen-activated protein kinase (MAPK), which decreases the ability of insulin to reduce gluconeogenesis.4 In murine models of obesity, hepatic p38 MAPK is activated and when p38 MAPK is overexpressed in the liver, impairment of insulin signalling ensues.5 Nevertheless, the role of p38 MAPK in FFA-induced hepatic insulin resistance in vivo has not been assessed. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.