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Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease.
Int J Mol Med. 2005 Oct; 16(4):631-5.IJ

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.

Authors+Show Affiliations

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. nakamuta@intmed3.med.kyushu-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16142397

Citation

Nakamuta, Makoto, et al. "Evaluation of Fatty Acid Metabolism-related Gene Expression in Nonalcoholic Fatty Liver Disease." International Journal of Molecular Medicine, vol. 16, no. 4, 2005, pp. 631-5.
Nakamuta M, Kohjima M, Morizono S, et al. Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med. 2005;16(4):631-5.
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), 631-5.
Nakamuta M, et al. Evaluation of Fatty Acid Metabolism-related Gene Expression in Nonalcoholic Fatty Liver Disease. Int J Mol Med. 2005;16(4):631-5. PubMed PMID: 16142397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. AU - Nakamuta,Makoto, AU - Kohjima,Motoyuki, AU - Morizono,Shusuke, AU - Kotoh,Kazuhiro, AU - Yoshimoto,Tsuyoshi, AU - Miyagi,Izuru, AU - Enjoji,Munechika, PY - 2005/9/6/pubmed PY - 2005/12/22/medline PY - 2005/9/6/entrez SP - 631 EP - 5 JF - International journal of molecular medicine JO - Int J Mol Med VL - 16 IS - 4 N2 - 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. SN - 1107-3756 UR - https://www.unboundmedicine.com/medline/citation/16142397/Evaluation_of_fatty_acid_metabolism_related_gene_expression_in_nonalcoholic_fatty_liver_disease_ L2 - https://www.spandidos-publications.com/ijmm/16/4/631 DB - PRIME DP - Unbound Medicine ER -