Fatty liver is a uniform and early response of the liver to ethanol consumption. Previously, fatty liver was considered benign, however, it is now known that fatty liver can increase sensitivity to hepatotoxins such as lipopolysaccharide (LPS) and high levels of fatty acids promote lipotoxicity [42–44]. Hence, there is a need to understand the mechanisms responsible for fatty liver production by ethanol. Early hypotheses for mechanisms responsible for fatty liver production by ethanol included redox state changes (elevated NADH) when ethanol was metabolized by alcohol dehydrogenase, elevated formation of acetyl CoA from ethanol/acetaldehyde oxidation and impairment of β-oxidation of fatty acids [37]. Recent studies by Crabb, You and colleagues have identified new mechanisms which regulate the synthesis and the oxidation of fatty acids as being central to how ethanol produces fatty liver. Ethanol has been shown to elevate levels of SREBP-1c, a master transcriptional regulator of lipogenic enzymes, but to lower levels of PPARα, a master transcriptional regulator of lipolytic enzymes. Decreased activation of AMPK by ethanol plays a role in these effects [38–41]. What remains unclear is how ethanol
