title: Endogenously elevated n-3 polyunsaturated fatty acids alleviate acute ethanol-induced liver steatosis.
abstract: Effective means for the prevention of alcohol-induced liver disease, a global health problem, have yet to be developed. We evaluated whether the high endogenous levels of omega-3 polyunsaturated acids (n-3 PUFA) in fat-1 transgenic mice could protect them against acute ethanol-induced liver steatosis. We induced alcoholic liver steatosis in 9-week-old male heterozygous fat-1 mice and their wild-type (WT) male littermates through three oral gavages of 60% ethanol at 4.7 g/kg body weight. Hepatic lipid accumulation was significantly increased in both alcohol treatment groups, but by much less in the fat-1 group compared with the WT group. Fat-1 mice exhibited significantly lower levels of total hepatic/plasma TG and plasma alanine aminotransferase activity. Accordingly, hepatic expression of lipogenesis-related genes (e.g., SREBP-1c, FAS, and SCD-1) and plasma levels of inflammatory cytokines (e.g., IL-6, TNF-α, and MCP-1) were reduced in the fat-1 mice. Furthermore, decreased hepatic expression of cytochrome P450 2E1 (CYP2E1) and increased hepatic levels of PPAR-α and HO-1 were observed in the fat-1 mice, compared to the WT mice. These findings show that elevated tissue n-3 PUFA protect against acute ethanol-induced liver steatosis in fat-1 mice, possibly through the down-regulation of hepatic lipogenesis, inflammatory response, and oxidative stress.
authors.affiliation: Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Biomedical Analysis Center, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D016207:Cytokines / Q000097:blood; D000431:Ethanol / Q000633:toxicity; D044943:Fatty Acid Desaturases / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000235:genetics* / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D016207:Cytokines; D015525:Fatty Acids, Omega-3; C466741:fat-1 protein, C elegans; D000431:Ethanol; D044943:Fatty Acid Desaturases
keywords: alcoholic liver steatosis; fat-1 mice; lipid metabolism; n-3 PUFA; oxidative stress