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PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty‐acid metabolic enzymes
Author(s) -
Seo Yeon Seok,
Kim Ji Hoon,
Jo Nam Young,
Choi Kyung Mook,
Baik Sei Hyun,
Park JongJae,
Kim Jae Seon,
Byun Kwan Soo,
Bak YoungTae,
Lee Chang Hong,
Kim AeRee,
Yeon Jong Eun
Publication year - 2008
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04819.x
Subject(s) - endocrinology , medicine , nonalcoholic fatty liver disease , beta oxidation , steatosis , fatty acid , fatty liver , fatty acid metabolism , peroxisome proliferator activated receptor , peroxisome , fatty acid synthase , agonist , carnitine , carnitine palmitoyltransferase i , fatty acid synthesis , lipid metabolism , biology , biochemistry , receptor , metabolism , disease
Background and Aims: In a previous study, the authors found that reduced expression of peroxisome proliferator‐activated receptor (PPAR)‐α might play an important role in developing nonalcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the effects of PPAR‐α and ‐γ agonists on NAFLD and verify the mechanisms underlying the PPAR‐α and ‐γ 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‐α agonist treatment group (group III), or PPAR‐γ 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)‐α were measured. Results: After 28 weeks treatment with PPAR‐α or ‐γ 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 β‐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 β‐oxidation enzymes was confined to FATP and MCAD in group IV. TNF‐α tended to be reduced in groups III and IV compared with group II. Conclusions: Treatment with PPAR agonists, especially a PPAR‐α agonist, improved the histological and biochemical parameters in the OLETF rat model by inducing fatty‐acid metabolic enzymes.