Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease.

Makoto Nakamuta, Motoyuki Kohjima, Shusuke Morizono, Kazuhiro Kotoh, Tsuyoshi Yoshimoto, Izuru Miyagi, Munechika Enjoji

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver dysfunction, and its prevalence has markedly increased; however, the mechanisms involved in the pathogenesis of NAFLD have not been thoroughly investigated in humans. In this study, we evaluated the expression of fatty acid metabolism-related genes in NAFLD. Real-time RT-PCR was performed using liver biopsy samples from 12 NAFLD patients. The target genes studied were: acetyl-CoA carboxylase (ACC) 1, ACC2, and fatty acid synthase (FAS) for the evaluation of de novo fatty acid synthesis; carnitine palmitoyltransferase 1a (CPT1a), long-chain acyl-CoA dehydrogenase (LCAD), and long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase alpha (HADHalpha) for beta-oxidation in the mitochondria; peroxisome proliferator-activated receptor- (PPAR-) alpha and cytochrome P450 2E1 (CYP2E1) for oxidation in peroxisomes and microsomes (endoplasmic reticulum) respectively; and diacylglycerol O-acyltransferase 1 (DGAT1), PPAR-gamma, and hormone sensitive lipase (HSL) for triglyceride synthesis and catalysis. In NAFLD, expression of ACC1 and ACC2, but not FAS was increased, indicating that de novo fatty acid synthesis is enhanced in NAFLD. In contrast, expression of CTP1a, a rate-limiting enzyme, was remarkably decreased, indicating that beta-oxidation in the mitochondria was decreased, although the expression of LCAD and HADHalpha was increased. Expression of PPAR-alpha was increased, whereas that of CYP2E1 was reduced. The expression of DGAT1, PPAR-gamma, and HSL was enhanced. These data suggest that in NAFLD, increased de novo synthesis and decreased beta-oxidation in the mitochondria lead to accumulation of fatty acids in hepatocytes, although the extent of oxidation in peroxisomes and microsomes remains unclear.

Original languageEnglish
Pages (from-to)631-635
Number of pages5
JournalInternational journal of molecular medicine
Volume16
Issue number4
Publication statusPublished - Oct 2005

All Science Journal Classification (ASJC) codes

  • Genetics

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    Nakamuta, M., Kohjima, M., Morizono, S., Kotoh, K., Yoshimoto, T., Miyagi, I., & Enjoji, M. (2005). Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. International journal of molecular medicine, 16(4), 631-635.