title: PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes.
abstract: OBJECTIVE
  In a previous study, the authors found that reduced expression of peroxisome proliferator-activated receptor (PPAR)-alpha might play an important role in developing nonalcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the effects of PPAR-alpha and -gamma agonists on NAFLD and verify the mechanisms underlying the PPAR-alpha and -gamma agonist-induced improvements by evaluating the hepatic gene expression profile involved in fatty-acid metabolism, using the Otsuka-Long Evans-Tokushima fatty (OLETF) rat.
  
  
  METHODS
  Rats were assigned to a control group (group I), fatty liver group (group II), PPAR-alpha agonist treatment group (group III), or PPAR-gamma agonist treatment group (group IV). Fasting blood glucose, total cholesterol, and triglycerides were measured. Liver tissues from each group were processed for histological and gene expression analysis. mRNAs of enzymes involved in fatty-acid metabolism and tumor necrosis factor (TNF)-alpha were measured.
  
  
  RESULTS
  After 28 weeks treatment with PPAR-alpha or -gamma agonist, steatosis of the liver was improved in groups III and IV compared with group II. Fasting blood glucose levels were significantly lower in groups III and IV than in group II. In group III, mRNA expression of fatty-acid beta-oxidation enzymes, such as fatty-acid transport protein (FATP), fatty-acid binding protein, carnitine palmitoyltransferase II, medium-chain acyl-CoA dehydrogenase (MCAD), long-chain acyl-CoA dehydrogenase, and acyl-CoA oxidase, was significantly increased. However, the treatment-induced modulation of fatty-acid beta-oxidation enzymes was confined to FATP and MCAD in group IV. TNF-alpha tended to be reduced in groups III and IV compared with group II.
  
  
  CONCLUSIONS
  Treatment with PPAR agonists, especially a PPAR-alpha agonist, improved the histological and biochemical parameters in the OLETF rat model by inducing fatty-acid metabolic enzymes.
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul, Korea.
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Nam Young
authors.initials: NY
authors.lastname: Jo
authors.forename: Kyung Mook
authors.initials: KM
authors.lastname: Choi
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Baik
authors.forename: Jong-Jae
authors.initials: JJ
authors.lastname: Park
authors.forename: Jae Seon
authors.initials: JS
authors.lastname: Kim
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Byun
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Bak
authors.forename: Chang Hong
authors.initials: CH
authors.lastname: Lee
authors.forename: AeRee
authors.initials: A
authors.lastname: Kim
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Yeon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy*; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use; D020869:Gene Expression Profiling; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011345:Fenofibrate