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British Journal of Nutrition British Journal of Nutrition

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Dietary trans 10, cis 12-conjugated linoleic acid reduces the expression of fatty acid oxidation and drug detoxification enzymes in mouse liver

Published online by Cambridge University Press:  01 January 2007

Reuven Rasooly ,
Darshan S. Kelley ,
Jeff Greg  and
Bruce E. Mackey
Reuven Rasooly
Affiliation:
Western Human Nutrition Research Center, ARS, USDA, Davis, CA, USA
Darshan S. Kelley*
Affiliation:
Western Human Nutrition Research Center, ARS, USDA, Davis, CA, USA
Jeff Greg
Affiliation:
Department of Pathology, University of California Medical Center, Sacramento, CA, USA
Bruce E. Mackey
Affiliation:
California, Western regional Research Center, ARS, USDA, Albany, CA, USA
*
*Corresponding author: Darshan Kelley, fax +1 530 752 5271, email dkelley@whnrc.usda.gov
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Abstract

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Mice fed diets containing trans 10, cis 12 (t10, c12)-conjugated linoleic acid (CLA) develop fatty livers and the role of hepatic fatty acid oxidation enzymes in this development is not well defined. We examined the effects of dietary cis 9, trans 11-CLA (c9, t11-CLA) and t10, c12-CLA on the expression of hepatic genes for fatty acid metabolism. Female mice, 8 weeks old, (six animals per group) were fed either a control diet or diets supplemented with 0·5 % c9, t11- or t10, c12-CLA for 8 weeks. DNA microarray analysis showed that t10, c12-CLA increased the expression of 278 hepatic genes and decreased those of 121 genes (>2-fold); c9, t11-CLA increased expression of twenty-two genes and decreased those of nine. Real-time PCR confirmed that t10, c12-CLA reduced by the expression of fatty acid oxidation genes including flavin monooxygenase (FMO)-3 95 %, cytochrome P450 (cyt P450) 69 %, carnitine palmitoyl transferase 1a 77 %, acetyl CoA oxidase (ACOX) 50 % and PPARα 65 %; it increased the expression of fatty acid synthase by 3·5-fold (P < 0·05 for all genes, except ACOX P = 0·08). It also reduced the enzymatic activity of hepatic microsomal FMO by 40 % and the FMO3 specific protein by 67 %. c9, t11-CLA reduced FMO3 and cyt P450 expression by 61 % (P = 0·001) and 38 % (P = 0·06) and increased steoryl CoA desaturase transcription by 5·9-fold (P = 0·07). Both decreased fatty acid oxidation and increased fatty acid synthesis seem to contribute to the CLA-induced fatty liver. Since FMO and cyt P450 are also involved in drug detoxification, suppression of the transcription of these genes by CLA may have other health consequences besides development of fatty liver.

Keywords

MicroarraysReal-time PCRCytochrome P450Flavin monooxygenaseCarnitine palmitoyl transferasePPARα
Type
Research Article
Information
British Journal of Nutrition , Volume 97 , Issue 1 , January 2007 , pp. 58 - 66
Copyright
Copyright © The Authors 2007

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Dietary trans 10, cis 12-conjugated linoleic acid reduces the expression of fatty acid oxidation and drug detoxification enzymes in mouse liver
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