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Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease.
J Gastroenterol Hepatol. 2004 Jul; 19(7):799-804.JG

Abstract

BACKGROUND

Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains poorly understood, metabolic syndrome associated with insulin resistance is the most reproducible factor in the development of NAFLD. Fat accumulation in hepatocytes results from an imbalance in the input, output and oxidation of fatty acid. Peroxisomes contain a battery of fatty acid oxidizing enzymes, the first of which, acyl-CoA oxidase (AOX), initiates the beta-oxidation spiral. One of the mammalian peroxisome proliferator-activated receptors (PPAR), PPAR-alpha, regulates the transcriptional expression of the enzymes involved in fatty acid beta-oxidation. The aim of the present study was to define the role of PPAR-alpha and AOX in the development of NAFLD using the Otsuka Long-Evans Tokushima fatty (OLETF) rat model.

METHODS

Liver tissue from OLETF (n = 12) and control (n = 10) rats 12, 28, and 40 weeks old were processed for histopathological and western blot analysis. The messenger RNA of PPAR-alpha and AOX were quantified by real-time RT-PCR.

RESULTS

At 40 weeks old, the histological analysis of the OLETF rat liver had steatosis (approximately 66%) and mild inflammation, which were comparable to those in NAFLD. Histological changes were unremarkable in 12 week and 28 week rats. In 12 week OLETF rats, the mRNA of AOX was 63% of the control. Expression of PPAR-alpha mRNA was also reduced to 3% that of the control. Along with the changes of mRNA, the protein expression of PPAR-alpha was also significantly reduced to 17% that of the control. In 28 week and 40 week animals, PPAR-alpha protein expression gradually increased to 75% and 78% that of the control. Expression of PPAR-alpha mRNA was also increased by up to 26% and 110% of the control. AOX, regulated by PPAR-alpha, also increased to 149% and 120% of the control.

CONCLUSION

Reduced expression of PPAR-alpha and AOX was observed even before definite steatosis had developed. The alteration of peroxisomal fatty acid metabolism may have an important role in the development of NAFLD.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea. je_yeon@hotmail.comNo 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

15209628

Citation

Yeon, Jong Eun, et al. "Reduced Expression of Peroxisome Proliferator-activated Receptor-alpha May Have an Important Role in the Development of Non-alcoholic Fatty Liver Disease." Journal of Gastroenterology and Hepatology, vol. 19, no. 7, 2004, pp. 799-804.
Yeon JE, Choi KM, Baik SH, et al. Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2004;19(7):799-804.
Yeon, J. E., Choi, K. M., Baik, S. H., Kim, K. O., Lim, H. J., Park, K. H., Kim, J. Y., Park, J. J., Kim, J. S., Bak, Y. T., Byun, K. S., & Lee, C. H. (2004). Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology, 19(7), 799-804.
Yeon JE, et al. Reduced Expression of Peroxisome Proliferator-activated Receptor-alpha May Have an Important Role in the Development of Non-alcoholic Fatty Liver Disease. J Gastroenterol Hepatol. 2004;19(7):799-804. PubMed PMID: 15209628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease. AU - Yeon,Jong Eun, AU - Choi,Kyung Mook, AU - Baik,Sei Hyun, AU - Kim,Kyoung Oh, AU - Lim,Hyoung Joon, AU - Park,Ki Ho, AU - Kim,Jin Yong, AU - Park,Jong-Jae, AU - Kim,Jae Seon, AU - Bak,Young-Tae, AU - Byun,Kwan Soo, AU - Lee,Chang Hong, PY - 2004/6/24/pubmed PY - 2004/12/16/medline PY - 2004/6/24/entrez SP - 799 EP - 804 JF - Journal of gastroenterology and hepatology JO - J Gastroenterol Hepatol VL - 19 IS - 7 N2 - BACKGROUND: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains poorly understood, metabolic syndrome associated with insulin resistance is the most reproducible factor in the development of NAFLD. Fat accumulation in hepatocytes results from an imbalance in the input, output and oxidation of fatty acid. Peroxisomes contain a battery of fatty acid oxidizing enzymes, the first of which, acyl-CoA oxidase (AOX), initiates the beta-oxidation spiral. One of the mammalian peroxisome proliferator-activated receptors (PPAR), PPAR-alpha, regulates the transcriptional expression of the enzymes involved in fatty acid beta-oxidation. The aim of the present study was to define the role of PPAR-alpha and AOX in the development of NAFLD using the Otsuka Long-Evans Tokushima fatty (OLETF) rat model. METHODS: Liver tissue from OLETF (n = 12) and control (n = 10) rats 12, 28, and 40 weeks old were processed for histopathological and western blot analysis. The messenger RNA of PPAR-alpha and AOX were quantified by real-time RT-PCR. RESULTS: At 40 weeks old, the histological analysis of the OLETF rat liver had steatosis (approximately 66%) and mild inflammation, which were comparable to those in NAFLD. Histological changes were unremarkable in 12 week and 28 week rats. In 12 week OLETF rats, the mRNA of AOX was 63% of the control. Expression of PPAR-alpha mRNA was also reduced to 3% that of the control. Along with the changes of mRNA, the protein expression of PPAR-alpha was also significantly reduced to 17% that of the control. In 28 week and 40 week animals, PPAR-alpha protein expression gradually increased to 75% and 78% that of the control. Expression of PPAR-alpha mRNA was also increased by up to 26% and 110% of the control. AOX, regulated by PPAR-alpha, also increased to 149% and 120% of the control. CONCLUSION: Reduced expression of PPAR-alpha and AOX was observed even before definite steatosis had developed. The alteration of peroxisomal fatty acid metabolism may have an important role in the development of NAFLD. SN - 0815-9319 UR - https://www.unboundmedicine.com/medline/citation/15209628/Reduced_expression_of_peroxisome_proliferator_activated_receptor_alpha_may_have_an_important_role_in_the_development_of_non_alcoholic_fatty_liver_disease_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2004&volume=19&issue=7&spage=799 DB - PRIME DP - Unbound Medicine ER -