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Effects of fatty acids on gene expression: role of peroxisome proliferator-activated receptor α, liver X receptor α and sterol regulatory element-binding protein-1c

Published online by Cambridge University Press:  28 July 2008

Sander Kersten
Sander Kersten
Affiliation:
Nutrition, Metabolism and Genomics Group, Wageningen University, PO Box 8129, 6700 EV Wageningen, The Netherlands
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Abstract

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Dietary fatty acids have numerous effects on cellular function, many of which are achieved by altering the expression of genes. The present paper reviews recent data on the mechanisms by which fatty acids influence DNA transcription, and focus specifically on the importance of three transcription factors: peroxisome proliferator-activated receptor α; liver X receptor α; sterol regulatory element-binding protein 1c. These data indicate that fatty acids induce or inhibit the mRNA expression of a variety of different genes by acting both as agonists and as antagonists for nuclear hormone receptors.

Keywords

Fatty acidsTranscription factorsmRNA expressionNuclear hormone receptors
Type
Joint National Nurses Nutritional Group and Parenteral and Enteral Group of the British Dietetic Association Symposium on ‘Working in Partnership’
Information
Proceedings of the Nutrition Society , Volume 61 , Issue 3 , August 2002 , pp. 371 - 374
Copyright
Copyright © The Nutrition Society 2002

References

Aoyama, T, Peters, JM, Iritani, N, Nakajima, T, Furihata, K, Hashimoto, T & Gonzalez, FJ (1998) Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PP ARalpha). Journal of Biological Chemistry 273, 5678–5684.Google Scholar
Clarke, SD & Jump, DB (1996) Polyunsaturated fatty acid regulation of hepatic gene transcription. Journal of Nutrition 126, 1105S–1109S.Google Scholar
Ellinghaus, P, Wolfrum, C, Assmann, G, Spener, F & Seedorf, U (1999) Phytanic acid activates the peroxisome proliferator-activated receptor alpha (PPARalpha) in sterol carrier protein 2-/sterol carrier protein x-deficient mice. Journal of Biological Chemistry 274, 2766–2772.Google Scholar
Escher, P, Braissant, O, Basu-Modak, S, Michalik, L, Wahli, W & Desvergne, B (2001) Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 142, 4195–4202.Google Scholar
Forman, BM, Chen, J & Evans, RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proceedings of the National Academy of Sciences USA 94, 4312–4317.Google Scholar
Hannah, VC, Ou, J, Luong, A, Goldstein, JL & Brown, MS (2001) Unsaturated fatty acids down-regulate srebp isoforms 1a and 1c by two mechanisms in HEK-293 cells. Journal of Biological Chemistry 276, 4365–4372.Google Scholar
Hashimoto, T, Cook, WS, Qi, C, Yeldandi, AV, Reddy, JK & Rao, MS (2000) Defect in peroxisome proliferator-activated receptor alpha-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. Journal of Biological Chemistry 275, 28918–28928.CrossRefGoogle ScholarPubMed
Hashimoto, T, Fujita, T, Usuda, N, Cook, W, Qi, C, Peters, JM, Gonzalez, FJ, Yeldandi, AV, Rao, MS & Reddy, JK (1999) Peroxisomal and mitochondrial fatty acid beta-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor alpha and peroxisomal fatty acyl-CoA oxidase. Genotype correlation with fatty liver phenotype. Journal of Biological Chemistry 274, 19228–19236.Google Scholar
Kersten, S, Mandard, S, Escher, P, Gonzalez, FJ, Tafuri, S, Desvergne, B & Wahli, W (2001) The peroxisome proliferator activated receptor alpha regulates amino acid metabolism. FASEB Journal 15, 1971–1978.Google Scholar
Kersten, S, Seydoux, J, Peters, JM, Gonzalez, FJ, Desvergne, B & Wahli, W (1999) Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. Journal of Clinical Investigation 103, 1489–1498.CrossRefGoogle ScholarPubMed
Kim, HJ, Takahashi, M & Ezaki, O (1999) Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mrnas. Journal of Biological Chemistry 274, 25892–25898.CrossRefGoogle ScholarPubMed
Kliewer, SA, Sundseth, SS, Jones, SA, Brown, PJ, Wisely, GB, Koble, CS, Devchand, P, Wahli, W, Willson, TM, Lenhard, JM & Lehmann, JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proceedings of the National Academy of Sciences USA 94, 4318–4323.Google Scholar
Krey, G, Braissant, O, L'Horset, F, Kalkhoven, E, Perroud, M, Parker, MG & Wahli, W (1997) Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Molecular Endocrinology 11, 779–791.CrossRefGoogle ScholarPubMed
Lee, SS, Pineau, T, Drago, J, Lee, EJ, Owens, JW, Kroetz, DL, Fernandez-Salguero, PM, Westphal, H & Gonzalez, FJ (1995) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Molecular and Cellular Biology 15, 3012–3022.Google Scholar
Leone, TC, Weinheimer, CJ & Kelly, DP (1999) A critical role forthe peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proceedings of the National Academy of Sciences USA 96, 7473–7478.CrossRefGoogle Scholar
Lin, Q, Ruuska, SE, Shaw, NS, Dong, D & Noy, N (1999) Ligand selectivity of the peroxisome proliferator-activated receptor alpha. Biochemistry 38, 185–190.CrossRefGoogle ScholarPubMed
Mater, MK, Thelen, AP, Pan, DA & Jump, DB (1999) Sterol response element-binding protein 1c (SREBP1c) is involved in the polyunsaturated fatty acid suppression of hepatic S14 gene transcription. Journal of Biological Chemistry 274, 32725–32732.CrossRefGoogle ScholarPubMed
Osborne, TF (2000) Sterol regulatory element-binding proteins (SREBPs): key regulators of nutritional homeostasis and insulin action. Journal of Biological Chemistry 275, 32379–32382.Google Scholar
Ou, J, Tu, H, Shan, B, Luk, A, Debose-Boyd, RA, Bashmakov, Y, Goldstein, JL & Brown, MS (2001) Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR. Proceedings of the National Academy of Sciences USA 98, 6027–6032.Google Scholar
Peters, JM, Hennuyer, N, Staels, B, Fruchart, JC, Fievet, C, Gonzalez, FJ & Auwerx, J (1997) Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice. Journal of Biological Chemistry 272, 27307–27312.Google Scholar
Ren, B, Thelen, A & Jump, DB (1996) Peroxisome proliferator-activated receptor alpha inhibits hepatic S14 gene transcription. Evidence against the peroxisome proliferator-activated receptor alpha as the mediator of polyunsaturated fatty acid regulation of s14 gene transcription. Journal of Biological Chemistry 271, 17167–17173.CrossRefGoogle ScholarPubMed
Ren, B, Thelen, AP, Peters, JM, Gonzalez, FJ & Jump, DB (1997) Polyunsaturated fatty acid suppression of hepatic fatty acid synthase and S14 gene expression does not require peroxisome proliferator-activated receptor alpha. Journal of Biological Chemistry 272, 26827–26832.Google Scholar
Repa, JJ, Liang, G, Ou, J, Bashmakov, Y, Lobaccaro, JM, Shimomura, I, Shan, B, Brown, MS, Goldstein, JL & Mangelsdorf, DJ (2000) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes and Development 14, 2819–2830.Google Scholar
Schultz, JR, Tu, H, Luk, A, Repa, JJ, Medina, JC, Li, L, Schwendner, S, Wang, S, Thoolen, M, Mangelsdorf, DJ, Lustig, KD & Shan, B (2000) Role of LXRs in control of lipogenesis. Genes and Development 14, 2831–2838.Google Scholar
Shimano, H, Horton, JD, Shimomura, I, Hammer, RE, Brown, MS & Goldstein, JL (1997) Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. Journal of Clinical Investigation 99, 846–854.Google Scholar
Thewke, DP, Panini, SR & Sinensky, M (1998) Oleate potentiates oxysterol inhibition of transcription from sterol regulatory element-1-regulated promoters and maturation of sterol regulatory element-binding proteins. Journal of Biological Chemistry 273, 21402–21407.CrossRefGoogle ScholarPubMed
Xu, HE, Lambert, MH, Montana, VG, Parks, DJ, Blanchard, SG, Brown, PJ, Sternbach, DD, Lehmann, JM, Wisely, GB, Wilson, TM, Kliewer, SA & Milburn, MV (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Molecular Cell 3, 397–403.CrossRefGoogle ScholarPubMed
Xu, J, Nakamura, MT, Cho, HP & Clarke, SD (1999) Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats. Journal of Biological Chemistry 274, 23577–23583.Google Scholar
Xu, J, Teran-Garcia, M, Park, JH, Nakamura, MT & Clarke, SD (2001) Polyunsaturated fatty acids suppress hepatic sterol regulatory element-binding protein-1 expression by accelerating transcript decay. Journal of Biological Chemistry 276, 9800–9807.CrossRefGoogle ScholarPubMed
Yahagi, N, Shimano, H, Hasty, AH, Amemiya-Kudo, M, Okazaki, H, Tamura, Y, Iizuka, Y, Shionoiri, F, Ohashi, K, Osuga, J, Harada, K, Gotoda, T, Nagai, R, Ishibashi, S & Yamada, N (1999) A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids. Journal of Biological Chemistry 274, 35840–35844.CrossRefGoogle ScholarPubMed
Yoshikawa, T, Shimano, H, Yahagi, N, Ide, T, Amemiya-Kudo, M, Matsuzaka, T, Nakakuki, M, Tomita, S, Okazaki, H, Tamura, Y, Iizuka, Y, Ohashi, K, Takahashi, A, Sone, H, Osuga, JJ, Gotoda, T, Ishibashi, S & Yamada, N (2002) Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXRresponse elements. Journal of Biological Chemistry 277, 1705–1711.CrossRefGoogle Scholar
Zomer, AW, Jansen, GA, Van Der, Burg B, Verhoeven, NM, Jakobs, C, Van Der, Saag PT, Wanders, RJ & Poll-The, BT (2000) Phytanoyl-CoA hydroxylase activity is induced by phytanic acid. European Journal of Biochemistry 267, 4063–4067.Google Scholar