Interestingly, under conditions of NAFLD-related hepatic insulin resistance, hepatic DNL remains activated in the absence of hepatic gluconeogenesis inhibition.320 Recently, after comparing obese NAFLD patients with obese-only patients, Horst discovered that the hepatic DNL increase is independent of hepatic insulin resistance and that the underlying molecular mechanism involves the activation of carbohydrate response element-binding protein (ChREBP). The gene discussed is MLXIPL; the disease is metabolic dysfunction-associated steatotic liver disease.