title: Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways.
abstract: Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA) that primarily regulates PGC1αand soy protein (SP) that seems to have its major regulatory effect on PGC1βwere evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or lowω3FA fish oil and soy protein. Low-ω3FA 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 PGC1αand their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1βand sterol regulatory element-binding protein 1c (SREBP1c) and their target lipogenic pathway genesviathe 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.
authors.affiliation: Lipid Research Laboratory, VA Medical Center and Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Reyes-Gordillo
authors.affiliation: Lipid Research Laboratory, VA Medical Center and Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Shah
authors.affiliation: Lipid Research Laboratory, VA Medical Center and Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Varatharajalu
authors.affiliation: Lipid Research Laboratory, VA Medical Center and Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, USA.
authors.forename: Mamatha
authors.initials: M
authors.lastname: Garige
authors.affiliation: Lipid Research Laboratory, VA Medical Center and Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, USA.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Leckey
authors.affiliation: Lipid Research Laboratory, VA Medical Center and Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC, USA.
authors.forename: M Raj
authors.identifier: 0000-0003-2415-4509
authors.initials: MR
authors.lastname: Lakshman
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000633:toxicity; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D005235:Fatty Liver, Alcoholic / Q000473:pathology* / Q000517:prevention & control; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D030262:Soybean Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D008055:Lipids; D008075:Lipoproteins, HDL; D056918:Nuclear Receptor Coactivators; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; C000604401:Ppargc1b protein, rat; D030262:Soybean Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D000431:Ethanol; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1