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

• Published in: Oxidative medicine and cellular longevity 2016, Vol.2016 (1), p.1840513
• Main Authors: Reyes-Gordillo, Karina, Shah, Ruchi, Varatharajalu, Ravi, Garige, Mamatha, Leckey, Leslie C, Lakshman, M Raj
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Ethanol - toxicity; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-3 - therapeutic use; Fatty Liver, Alcoholic - pathology; Fatty Liver, Alcoholic - prevention & control; Female; Lipid Peroxidation - drug effects; Lipids - analysis; Lipids - blood; Lipoproteins, HDL - blood; Liver - metabolism; Nuclear Receptor Coactivators - genetics; Nuclear Receptor Coactivators - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; PPAR gamma - genetics; PPAR gamma - metabolism; Rats; Rats, Wistar; Signal Transduction - drug effects; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Soybean Proteins - pharmacology; Soybean Proteins - therapeutic use; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2016/1840513

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.