Title: DIETARY T10, C-12-CONJUGATED LINOLEIC ACID REDUCES THE EXPRESSION OF FATTY ACID OXIDATION AND DRUG DETOXIFICATION ENZYMES IN MOUSE LIVER Authors
Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 28, 2006
Publication Date: January 1, 2007
Repository URL: http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN97_01%2FS0007114507257745a.pdf&code=fe89d1064159b083a467b20ce538f628
Citation: Rasooly, R., Kelley, D.S., Greg, J., Mackey, B.E. Dietary t10, c-12-conjugated linoleic acid reduces the expression of fatty acid oxidation and drug detoxification enzymes in mouse liver. Journal of Nutrition. 97:58-66, 2007. Interpretive Summary: Conjugated linoleic acid (CLA) is a collective term for a group of isomers of linoleic acid that have conjugated double bonds. There are several isomers of CLA; some like c9, t11-CLA are found in dairy products and ruminant meat, while others like t10, c12-CLA are found in margarines and hydrogenated oils. Feeding a mixture of CLA isomers or purified t10, c12-CLA causes the development of fatty liver in mice. Mechanisms that lead to the development of fatty liver by CLA are not understood. The purpose of this study was to examine the effects of two purified isomers of dietary CLA on the expression of mouse liver genes. Eight week old, female mice (n=6/group) were fed either a control diet, or diets supplemented with 0.5% c9, t11-CLA or t10, c12-CLA isomers for eight weeks. DNA microarrays and real-time PCR were used to determine changes in gene transcription. t10, c12-CLA increased the transcription of 278 hepatic genes (>2 fold) including 4 genes involved in fatty acid synthesis, and decreased those of 121 genes, including 5 genes involved in fatty acid oxidation. In addition, this isomer also reduced the expression and activity of drug detoxification enzymes. c9, t11-CLA increased expression of 22 genes and decreased those of 9. Our results suggest that both increased fatty acid synthesis and reduced fatty acid oxidation. Contribute to the development of fatty liver caused by t10, c12-CLA. Suppression of the drug detoxification enzymes by CLA may have other health consequences besides the development of fatty liver.
Technical Abstract: Mice fed diets containing t10, c12-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 c9, t11-CLA and t10, c12-CLA on the expression of hepatic genes for fatty acid metabolism. Eight week old, female mice (n=6/group) were fed either a control diet, or diets supplemented with 0.5% c9, t11- or t10, c12-CLA for eight weeks. DNA microarrays analysis showed that t10, c12-CLA increased the transcription of 278 hepatic genes, and decreased those of 121 genes (>2 fold); c9, t11-CLA increased expression of 22 genes and decreased those of 9. Real-time PCR analysis was used to confirm the changes in the expression of lipid metabolism genes. Dietary t10, c12-CLA reduced the transcription of fatty acid oxidation genes including, flavin monooxygenase3 (FMO) 95%, cytochrome P450 (P450) 69%, carnitne palmitoyl transferase 77%, acetyl CoA oxidase (ACOX) 50 %, and peroxisomal proliferators activated receptor a 65%; it increased the transcription 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 P450 transcription by 61 and 38%, and increased steoryl CoA desaturase transcription by 5.9 fold. Both decreased fatty acid oxidation and increased fatty acid synthesis seem to contribute to the CLA-induced fatty liver. Since FMO and P450 are also involved in drug detoxification, suppression of the transcription of these genes by CLA may have other health consequences besides the development of fatty liver.