Low-omega 3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1 beta) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-omega 3 fatty acid (Low-omega 3FA) that primarily regulates PGC1 alpha and soy protein (SP) that seems to have its major regulatory effect on PGC1 beta were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low omega 3FA fish oil and soy protein. Low-omega 3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1) and PGC1 alpha and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1 alpha and sterol regulatory element-binding protein 1c (SREBP1c) and their target lipogenic pathway genes via the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK). Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.