Low-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) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-3 fatty acid (Low-3FA) that primarily regulates PGC1 and soy protein (SP) that seems to have its major regulatory effect on PGC1 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 3FA fish oil and soy protein. Low-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 and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1 and sterol regulatory element-binding protein 1c (SREBP1c) and their target lipogenic pathway genes 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.