Chronic ethanol feeding downregulates hepatic AMPK signaling. This inhibition promotes SREBP-1 activity, leading to increased total lipin-1, and favors production of cytosolic lipin-1, resulting in increased PAP activity and TG synthesis in mouse livers. We further speculate that ethanol affects lipin-1’s role in regulating FA oxidation. The net consequence of these changes is to promote hepatic steatosis. AMPK, AMP-activated protein kinase; ER, endoplasmic reticulum; SREBP-1, sterol regulatory element binding protein1. PAP, phosphatidate phosphatase type; PPAR, peroxisome proliferator-activated receptor; PGC-1α, PPARγ co-activator-alpha; TG, triglyceride.