title: Down-regulation in muscle and liver lipogenic genes: EPA ethyl ester treatment in lean and overweight (high-fat-fed) rats.
abstract: The precise mechanisms by which omega-3 fatty acids improve fat metabolism are not completely understood. This study was designed to determine the effects of eicosapentaenoic acid (EPA) ethyl ester administration on the expression levels of several muscle, liver and adipose tissue genes involved in lipogenesis and fatty acid oxidation pathways. Male Wistar rats fed a standard diet (control animals) or a high-fat diet were treated daily by oral gavage with EPA ethyl ester (1g/kg) for 5 weeks. The high-fat diet caused a very significant increase in plasma cholesterol (P<.01) levels, which was reverted by EPA (P<.001). A significant decrease in circulating triglyceride levels (P<.05) was also observed in EPA-treated groups. EPA administration induced a significant down-regulation in some lipogenic genes such as muscle acetyl CoA carboxylase beta (ACC beta) (P<.05) and liver fatty acid synthase (FAS) (P<.05). Furthermore, a decrease in glucokinase (GK) gene expression was observed in EPA-treated animals fed a control diet (P<.01), whereas a significant increase in GK mRNA levels was found in groups fed a high-fat diet. On the other hand, no alterations in genes involved in beta-oxidation, such acetyl CoA synthase 4 (ACS4), acetyl CoA synthase 5 (ACS5) or acetyl CoA oxidase (ACO), were found in EPA-treated groups. Surprisingly and opposite to the expectations, a very significant decrease in the expression levels of liver PPARalpha (P<.01) was observed after EPA treatment. These findings show the ability of EPA ethyl ester treatment to down-regulate some genes involved in fatty acid synthesis without affecting the transcriptional activation of beta-oxidation-related genes.
authors.affiliation: Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Pérez-Echarri
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.forename: Beatriz
authors.initials: B
authors.lastname: Marcos-Gómez
authors.forename: Amelia
authors.initials: A
authors.lastname: Marti
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.forename: María J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D015536:Down-Regulation; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D007657:Ketone Bodies / Q000097:blood; D008055:Lipids / Q000008:administration & dosage; D050155:Lipogenesis / Q000235:genetics*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013851:Thinness / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis / Q000097:blood
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D008055:Lipids; D047493:PPAR alpha; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; D015118:Eicosapentaenoic Acid; D064429:Fatty Acid Synthases; D005941:Glucokinase; D000103:Acetyl-CoA Carboxylase