Hepatic steatosis can evolve into non-alcoholic fatty liver disease (NAFLD). Monocarboxylate transporter isoform 1 (MCT1) haploinsufficient mice (MCT1+/-) exhibit resistance to high-fat diet-induced obesity and associated NAFLD. Carneiro et al. reinforce the concept that AMP-activated protein kinase (AMPK) activation mediates this effect and promotes a protection against hepatic steatosis by inhibiting Sterol Regulatory Element Binding Protein 1 (SREBP1). They also reveal an unexpected regulatory role of circulating lactate in the regulation of hepatic lipid metabolism.