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PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes.
J Gastroenterol Hepatol. 2008 Jan; 23(1):102-9.JG

Abstract

BACKGROUND AND AIMS

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+Show Affiliations

Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18171348

Citation

Seo, Yeon Seok, et al. "PPAR Agonists Treatment Is Effective in a Nonalcoholic Fatty Liver Disease Animal Model By Modulating Fatty-acid Metabolic Enzymes." Journal of Gastroenterology and Hepatology, vol. 23, no. 1, 2008, pp. 102-9.
Seo YS, Kim JH, Jo NY, et al. PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes. J Gastroenterol Hepatol. 2008;23(1):102-9.
Seo, Y. S., Kim, J. H., Jo, N. Y., Choi, K. M., Baik, S. H., Park, J. J., Kim, J. S., Byun, K. S., Bak, Y. T., Lee, C. H., Kim, A., & Yeon, J. E. (2008). PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes. Journal of Gastroenterology and Hepatology, 23(1), 102-9. https://doi.org/10.1111/j.1440-1746.2006.04819.x
Seo YS, et al. PPAR Agonists Treatment Is Effective in a Nonalcoholic Fatty Liver Disease Animal Model By Modulating Fatty-acid Metabolic Enzymes. J Gastroenterol Hepatol. 2008;23(1):102-9. PubMed PMID: 18171348.
* Article titles in AMA citation format should be in sentence-case
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 - 2008/1/4/pubmed PY - 2008/3/6/medline PY - 2008/1/4/entrez SP - 102 EP - 9 JF - Journal of gastroenterology and hepatology JO - J Gastroenterol Hepatol VL - 23 IS - 1 N2 - BACKGROUND AND AIMS: 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. SN - 1440-1746 UR - https://www.unboundmedicine.com/medline/citation/18171348/PPAR_agonists_treatment_is_effective_in_a_nonalcoholic_fatty_liver_disease_animal_model_by_modulating_fatty_acid_metabolic_enzymes_ L2 - https://doi.org/10.1111/j.1440-1746.2006.04819.x DB - PRIME DP - Unbound Medicine ER -