The effects of alcohol metabolism on histone acetylation have been demonstrated in animal experiments, including studies of obese mice.2 Alcohol administration to these animals was associated with exacerbation of fatty liver, which resulted from an impairment of the hepatic lipid metabolism pathways, mainly those mediated by SIRT1 and AMPK (Everitt et al. 2012). The development of alcohol-induced fatty liver could be prevented by administering rosiglitazone, an anti-diabetic medication that binds to certain receptors in fat cells and makes them more sensitive to insulin. The protective effect of rosiglitazone was attributed to its enhancement of the hepatic adiponectin–SIRT1–AMPK signaling pathway (Shen et al. 2010). Other studies found that chronic alcohol consumption can result in protein hyper-acetylation within cell components called mitochondria. Most proteins in the mitochondria normally are deacetylated through SIRT3-dependent mechanisms (Fritz et al. 2012). Ethanol-induced suppression of SIRT3 and the concomitant increase of another acetylation pathway (i.e., cyclophilin-D acetylation) could be prevented by AMPK activation (Shulga and Pasorino 2010). The role of alcohol metabolism in histone acetylation is shown in figure 3.
