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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

  • Reuven Rasooly (a1), Darshan S. Kelley (a1), Jeff Greg (a2) and Bruce E. Mackey (a3)
Abstract

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.

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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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      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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Corresponding author
*Corresponding author: Darshan Kelley, fax +1 530 752 5271, email dkelley@whnrc.usda.gov
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MA Belury (2002) Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action. Ann Rev Nutr 22, 505531

MA Belury & A Kempa-Steczko (1997) Conjugated linoleic acid modulates hepatic lipid composition in mice. Lipids 32, 199204

JR Cashman & J Proudfoot (1988) A reverse-phase liquid chromatographic assay for flavin-containing monooxygenase activity. Analytical Biochemistry 175, 274280

WG Chung & DR Buhler (1994) The effect of spironolactone treatment on the cytochrome P450-mediated metabolism of the pyrrolizidine alkaloid senecionine by hepatic microsomes from rats and guinea pigs. Toxicology and Applied Pharmacology 127, 314319

L Clement , H Poirer & I Noit (2002) Dietary trans-10, cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in mouse. J. Lipid Res 43, 14001409

P Degrace , L Demizieux & J Gresti (2003) Association of liver steatosis with lipid oversecretion and hypotriglyceridaemia in C57BL/6J mice fed trans-10, cis-12 linoleic acid. FEBS Letters 546, 335339

L Demizieux , P Degrace & J Gresti (2002) Conjugated linoleic acid isomers in mitochondria: evidence for an alteration of fatty acid oxidation. J. Lipid Res 43, 21122122

K Eulitz , MP Yurawecz , N Sehat , J Fritsche , JAG Roach , MM Mossoba , JKG Kramer , RO Adlof & Y Ku (1999) Preparation, separation, and confirmation of the eight geometrical cis/trans conjugated linoleic acid isomers, 8,10 through 11, 13–18:2. Lipids 34, 873877

JG Falls , NJ Cherrington & KM Clements (1997) Molecular cloning, sequencing, and expression of Escherichia coli of mouse flavin-containing monooxygenase 3 (FMO3): comparison with human isoform. Achieves of Biochemistry and Biophysics 347, 918

T Ide (2005) Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue. Diabetes 54, 412423

M Javadi , AC Beynen & R Hovenier (2004) Prolonged feeding of mice with conjugated linoleic acid increases hepatic fatty acid synthesis relative to oxidation. Journal of Nutritional Biochemistry 15, 680687

SK Krueger , JE Vandyke , DE Williams & RN Hines (2006) The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines. Drug Metab Rev 38, 139147

SK Krueger & DE Williams (2005) Mammalian flavin-containing monooxygenases:structure/function, genetic polymorphisms and role in drug metabolism. Pharmacology and Therapeutics 106, 357387

M Orellana , R Rodrigo & E Valdes (1998) Peroxisomal and microsomal fatty acid oxidation in liver of rats after chronic ethanol consumption. Gen Pharmac 31, 817820

Y Park , JM Storkson , KJ Albright , W Liu & MW Pariza (1999) Evidence that trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 34, 235241

H Poirier , C Rouault & L Clement (2005) Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated with decrease in leptin and adiponectin plasma levels and pancreatic beta cell hyperplasia in the mouse. Diabetologia 48, 10591065

JK Reddy & T Hashimoto (2001) Peroxisomal b-oxidation and peroxisome proliferator-activated receptor a: an adaptive metabolic system. Ann Rev Nutr 21, 193230

RJ Sanders , R Ofman , F Valianpour , S Kemp & RJ Wanders (2005) Evidence of two enzymatic pathways for ω-oxidation of docosanoic acid in rat liver microsomes. J Lipid Res 46, 10011008

S Tricon , GC Burdge , CM Williams , PC Calder & P Yaqoob (2005) The effects of conjugated linoleic acid on human health-related outcomes. Proc Nutr Soc 64, 171182

N Tsuboyama-Kasaoka , M Takahashi , K Tanemura , HJ Kim , T Tange , H Okuyama , M Kasai , I Shinji & O Ezaki (2000) Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 49, 15341542

JM Warren , VA Simon , G Bartolini , KL Erickson , BE Mackey & DS Kelley (2003) Trans-10, cis-12 CLA increases liver and decreases adipose tissue lipids in mice: Possible role of specific lipid metabolism genes. Lipids 38, 497504

Y Weng , CC DiRusso , AA Reilly , PN Blacks & X Ding (2005) Hepatic gene expression changes in mouse models with liver-specific deletion or global suppression of the NADPH-cytochrome P450 reductase gene. J Biol Chem 280, 3168631698

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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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