Dietary trans 10, cis 12-conjugated linoleic acid reduces the expression of fatty acid oxidation and drug detoxification enzymes in mouse liver.
Mice fed diets containing trans 10, cis 12 (t10, c12)-conjugated linoleic acid (CLA) develop fatty livers and the role of the 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 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 PPARalpha 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.
Rasooly
Reuven
R
Western Human Nutrition Research Center, ARS, USDA, Davis, CA, USA.
Kelley
Darshan S
DS
Greg
Jeff
J
Mackey
Bruce E
BE
D000821:Animal Feed; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D047468:Immunoprecipitation; D008658:Inactivation, Metabolic / Q000235:genetics*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; C496197:trans-10,cis-12-conjugated linoleic acid; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)