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Proc Natl Acad Sci U S A. Sep 3, 1996; 93(18): 9443–9448.

Peroxisome proliferators induce mouse liver stearoyl-CoA desaturase 1 gene expression.


Peroxisome proliferators induce stearoyl-CoA desaturase activity (EC in liver [Kawashima, Y., Hanioka, N., Matsumura, M. & Kozuka, H. (1983) Biochim. Biophys. Acta 752, 259-264]. We analyzed the changes in stearoyl-CoA desaturase 1 (SCD1) mRNA to further define the molecular mechanism for the induction of stearoyl-CoA desaturase by peroxisome proliferators. SCD1 mRNA was analyzed from the livers of BALB/c mice that had been fed diets supplemented with clofibrate or gemfibrozil. Clofibrate was found to induce liver SCD1 mRNA levels 3-fold within 6 hr to a maximum of 22-fold in 30 hr. Gemfibrozil administration resulted in a similar induction pattern. This induction is primarily due to an increase in transcription of the SCD1 gene, as shown by nuclear run-on transcription assays and DNA deletion analysis of transfected SCD1-chloramphenicol acetyltransferase fusion genes. The cis-linked response element for peroxisome proliferator-activated receptor (PPAR) was localized to an AGGTCA consensus sequence between base pairs -664 to -642 of the SCD1 promoter. Clofibrate-mediated induction of SCD1 mRNA was shown to be independent of polyunsaturated fatty acids, with peroxisome proliferators and arachidonic acid having opposite effects on SCD1 mRNA levels. Additionally, the activation of SCD1 mRNA by clofibrate was inhibited 77% by cycloheximide administration. Levels of liver beta-actin and albumin mRNAs were unchanged by these dietary manipulations. Our data show that hepatic SCD1 gene expression is regulated by PPARs and suggest that peroxisome proliferators and poly-unsaturated fatty acids act through distinct mechanisms.

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  • Reddy JK, Lalwai ND. Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. Crit Rev Toxicol. 1983;12(1):1–58. [PubMed]
  • Marcus SL, Miyata KS, Zhang B, Subramani S, Rachubinski RA, Capone JP. Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5723–5727. [PMC free article] [PubMed]
  • Alvares K, Fan C, Dadras SS, Yeldandi AV, Rachubinski RA, Capone JP, Subramani S, Iannaccone PM, Rao MS, Reddy JK. An upstream region of the enoyl-coenzyme A hydratase/3-hydroxyacyl-coenzyme A dehydrogenase gene directs luciferase expression in liver in response to peroxisome proliferators in transgenic mice. Cancer Res. 1994 May 1;54(9):2303–2306. [PubMed]
  • Muerhoff AS, Griffin KJ, Johnson EF. The peroxisome proliferator-activated receptor mediates the induction of CYP4A6, a cytochrome P450 fatty acid omega-hydroxylase, by clofibric acid. J Biol Chem. 1992 Sep 25;267(27):19051–19053. [PubMed]
  • Jump DB, Ren B, Clarke S, Thelen A. Effects of fatty acids on hepatic gene expression. Prostaglandins Leukot Essent Fatty Acids. 1995 Feb-Mar;52(2-3):107–111. [PubMed]
  • Kawashima Y, Mizuguchi H, Musoh K, Kozuka H. The mechanism for the increased supply of phosphatidylcholine for the proliferation of biological membranes by clofibric acid, a peroxisome proliferator. Biochim Biophys Acta. 1994 Jun 2;1212(3):311–318. [PubMed]
  • Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990 Oct 18;347(6294):645–650. [PubMed]
  • Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell. 1992 Mar 6;68(5):879–887. [PubMed]
  • Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994 May 15;8(10):1224–1234. [PubMed]
  • Zhu Y, Alvares K, Huang Q, Rao MS, Reddy JK. Cloning of a new member of the peroxisome proliferator-activated receptor gene family from mouse liver. J Biol Chem. 1993 Dec 25;268(36):26817–26820. [PubMed]
  • Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K, Evans RM. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355–7359. [PMC free article] [PubMed]
  • Göttlicher M, Widmark E, Li Q, Gustafsson JA. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4653–4657. [PMC free article] [PubMed]
  • Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry. 1993 Jun 1;32(21):5598–5604. [PubMed]
  • Kawashima Y, Hanioka N, Matsumura M, Kozuka H. Induction of microsomal stearoyl-CoA desaturation by the administration of various peroxisome proliferators. Biochim Biophys Acta. 1983 Jul 12;752(2):259–264. [PubMed]
  • Kawashima Y, Musoh K, Kozuka H. Peroxisome proliferators enhance linoleic acid metabolism in rat liver. Increased biosynthesis of omega 6 polyunsaturated fatty acids. J Biol Chem. 1990 Jun 5;265(16):9170–9175. [PubMed]
  • Tebbey PW, Buttke TM. Arachidonic acid regulates unsaturated fatty acid synthesis in lymphocytes by inhibiting stearoyl-CoA desaturase gene expression. Biochim Biophys Acta. 1992 Nov 15;1171(1):27–34. [PubMed]
  • Birnboim HC, Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. [PMC free article] [PubMed]
  • Thiede MA, Strittmatter P. The induction and characterization of rat liver stearyl-CoA desaturase mRNA. J Biol Chem. 1985 Nov 25;260(27):14459–14463. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. [PMC free article] [PubMed]
  • Ntambi JM. Dietary regulation of stearoyl-CoA desaturase 1 gene expression in mouse liver. J Biol Chem. 1992 May 25;267(15):10925–10930. [PubMed]
  • Kadesch T, Berg P. Effects of the position of the simian virus 40 enhancer on expression of multiple transcription units in a single plasmid. Mol Cell Biol. 1986 Jul;6(7):2593–2601. [PMC free article] [PubMed]
  • Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413–7417. [PMC free article] [PubMed]
  • Kaestner KH, Ntambi JM, Kelly TJ, Jr, Lane MD. Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase. J Biol Chem. 1989 Sep 5;264(25):14755–14761. [PubMed]
  • Tugwood JD, Issemann I, Anderson RG, Bundell KR, McPheat WL, Green S. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene. EMBO J. 1992 Feb;11(2):433–439. [PMC free article] [PubMed]
  • Castelein H, Gulick T, Declercq PE, Mannaerts GP, Moore DD, Baes MI. The peroxisome proliferator activated receptor regulates malic enzyme gene expression. J Biol Chem. 1994 Oct 28;269(43):26754–26758. [PubMed]
  • Landschulz KT, Jump DB, MacDougald OA, Lane MD. Transcriptional control of the stearoyl-CoA desaturase-1 gene by polyunsaturated fatty acids. Biochem Biophys Res Commun. 1994 Apr 29;200(2):763–768. [PubMed]
  • Hertz R, Kalderon B, Bar-Tana J. Thyromimetic effect of peroxisome proliferators. Biochimie. 1993;75(3-4):257–261. [PubMed]
  • Kochan Z, Bukato G, Swierczynski J. Inhibition of lipogenesis in rat brown adipose tissue by clofibrate. Biochem Pharmacol. 1993 Oct 19;46(8):1501–1506. [PubMed]
  • Kawashima Y, Hirose A, Kozuka H. Modification by clofibric acid of acyl composition of glycerolipids in rat liver. Possible involvement of fatty acid chain elongation and desaturation. Biochim Biophys Acta. 1984 Oct 4;795(3):543–551. [PubMed]
  • Reddy JK, Krishnakantha TP. Hepatic peroxisome proliferation: induction by two novel compounds structurally unrelated to clofibrate. Science. 1975 Nov 21;190(4216):787–789. [PubMed]
  • Reddy JK, Mannaerts GP. Peroxisomal lipid metabolism. Annu Rev Nutr. 1994;14:343–370. [PubMed]
  • Jeffcoat R. The biosynthesis of unsaturated fatty acids and its control in mammalian liver. Essays Biochem. 1979;15:1–36. [PubMed]
  • Blake WL, Clarke SD. Suppression of rat hepatic fatty acid synthase and S14 gene transcription by dietary polyunsaturated fat. J Nutr. 1990 Dec;120(12):1727–1729. [PubMed]
  • Girard J, Perdereau D, Foufelle F, Prip-Buus C, Ferré P. Regulation of lipogenic enzyme gene expression by nutrients and hormones. FASEB J. 1994 Jan;8(1):36–42. [PubMed]
  • Keller H, Mahfoudi A, Dreyer C, Hihi AK, Medin J, Ozato K, Wahli W. Peroxisome proliferator-activated receptors and lipid metabolism. Ann N Y Acad Sci. 1993 Jun 11;684:157–173. [PubMed]
  • Reddy JK, Goel SK, Nemali MR, Carrino JJ, Laffler TG, Reddy MK, Sperbeck SJ, Osumi T, Hashimoto T, Lalwani ND, et al. Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1747–1751. [PMC free article] [PubMed]

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