PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes

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Abstract

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.

Original languageEnglish
Pages (from-to)102-109
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume23
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1

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Peroxisome Proliferator-Activated Receptors
Fatty Acids
Animal Models
Enzymes
Fatty Acid Transport Proteins
Inbred OLETF Rats
Acyl-CoA Dehydrogenase
Fatty Liver
Blood Glucose
Fasting
Long-Chain Acyl-CoA Dehydrogenase
Tumor Necrosis Factor-alpha
Acyl-CoA Oxidase
Carnitine O-Palmitoyltransferase
Fatty Acid-Binding Proteins
Messenger RNA
Pseudogenes
Non-alcoholic Fatty Liver Disease
Liver
Transcriptome

Keywords

  • Insulin resistance
  • Nonalcoholic fatty liver
  • Peroxisome proliferator- activated receptors
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

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title = "PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes",
abstract = "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.",
keywords = "Insulin resistance, Nonalcoholic fatty liver, Peroxisome proliferator- activated receptors, Tumor necrosis factor",
author = "Seo, {Yeon Seok} and Kim, {Ji Hoon} and Jo, {Nam Young} and Choi, {Kyung Mook} and Sei-Hyun Baik and Park, {Jong Jae} and Kim, {Jae Seon} and Byun, {Kwan Soo} and Young-Tae Bak and Lee, {Chang Hong} and Aeree Kim and Yeon, {Jong Eun}",
year = "2008",
month = "1",
day = "1",
doi = "10.1111/j.1440-1746.2006.04819.x",
language = "English",
volume = "23",
pages = "102--109",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
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TY - JOUR

T1 - PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes

AU - Seo, Yeon Seok

AU - Kim, Ji Hoon

AU - Jo, Nam Young

AU - Choi, Kyung Mook

AU - Baik, Sei-Hyun

AU - Park, Jong Jae

AU - Kim, Jae Seon

AU - Byun, Kwan Soo

AU - Bak, Young-Tae

AU - Lee, Chang Hong

AU - Kim, Aeree

AU - Yeon, Jong Eun

PY - 2008/1/1

Y1 - 2008/1/1

N2 - 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.

AB - 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.

KW - Insulin resistance

KW - Nonalcoholic fatty liver

KW - Peroxisome proliferator- activated receptors

KW - Tumor necrosis factor

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U2 - 10.1111/j.1440-1746.2006.04819.x

DO - 10.1111/j.1440-1746.2006.04819.x

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EP - 109

JO - Journal of Gastroenterology and Hepatology (Australia)

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