Chronic exposure to ethanol inhibits the activity and/or downregulates the expression of several lipid metabolism regulating enzymes, foremost AMP-activated kinase (AMPK) [27], peroxisome proliferator activated receptors (PPARs) [28], retinoid X receptors (RXRs) [29], and sirtuin1 (SIRT1) and 5 (SIRT5) [30, 31], whereas up-regulates the sterol regulatory element-binding protein 1 (SREBP-1) [32]. The mechanisms by which ethanol consumption causes accumulation of hepatic triacylglycerols are complex. AMP-activated protein kinase (AMPK) has a pivotal role in the regulation of lipid metabolism; its activation increases fatty acid oxidation and reduces their synthesis. AMPK activity in liver of ethanol-fed rats is decreased and less sensitive to changes in the AMP/ATP ratio facilitating triacylglycerol accumulation [27]. Activation of SREBP-1 by ethanol feeding is associated with increased expression of hepatic lipogenic genes as well as the accumulation of triglycerides in the livers [32].
