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Transcriptional Regulation

Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor γ Expression

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Pages 3430-3444 | Received 22 Sep 2003, Accepted 19 Jan 2004, Published online: 27 Mar 2023

REFERENCES

  • Akiyama, T. E., Sakai S., Lambert G., Nicol C. J., Matsusue K., Pimprale S., Lee Y. H., Ricote M., Glass C. K., Brewer H. B., Jr., and Gonzalez F. J.. 2002. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol. Cell. Biol. 22:2607–2619.
  • Amemiya-Kudo, M., H. Shimano, T. Yoshikawa, N. Yahagi, A. H. Hasty, H. Okazaki, Y. Tamura, F. Shionoiri, Y. Iizuka, K. Ohashi, J. Osuga, K. Harada, T. Gotoda, R. Sato, S. Kimura, S. Ishibashi, and N. Yamada. 2000. Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene. J. Biol. Chem. 275:31078–31085.
  • Barak, Y., Nelson M. C., Ong E. S., Jones Y. Z., Ruiz-Lozano P., Chien K. R., Koder A., and Evans R. M.. 1999. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol. Cell 4:585–595.
  • Cao, G., Liang Y., Broderick C. L., Oldham B. A., Beyer T. P., Schmidt R. J., Zhang Y., Stayrook K. R., Suen C., Otto K. A., Miller A. R., Dai J., Foxworthy P., Gao H., Ryan T. P., Jiang X. C., Burris T. P., Eacho P. I., and Etgen G. J.. 2003. Antidiabetic action of a liver X receptor agonist mediated by inhibition of hepatic gluconeogenesis. J. Biol. Chem. 278:1131–1136.
  • Chawla, A., Boisvert W. A., Lee C. H., Laffitte B. A., Barak Y., Joseph S. B., Liao D., Nagy L., Edwards P. A., Curtiss L. K., Evans R. M., and Tontonoz P.. 2001. A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol. Cell 7:161–171.
  • Chawla, A., Repa J. J., Evans R. M., and Mangelsdorf D. J.. 2001. Nuclear receptors and lipid physiology: opening the X-files. Science 294:1866–1870.
  • Chawla, A., Saez E., and Evans R. M.. 2000. “Don't know much bile-ology. ” Cell 103:1–4.
  • Costet, P., Luo Y., Wang N., and Tall A. R.. 2000. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J. Biol. Chem. 275:28240–28245.
  • DeBose-Boyd, R. A., J. Ou, J. L. Goldstein, and M. S. Brown. 2001. Expression of sterol regulatory element-binding protein 1c (SREBP-1c) mRNA in rat hepatoma cells requires endogenous LXR ligands. Proc. Natl. Acad. Sci. USA 98:1477–1482.
  • DeFronzo, R. A. 1997. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis. Neth. J. Med. 50:191–197.
  • Edwards, P. A., Kast H. R., and Anisfeld A. M.. 2002. BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis. J. Lipid Res. 43:2–12.
  • Flier, J. S. 1995. The adipocyte: storage depot or node on the energy information superhighway? Cell 80:15–18.
  • Foretz, M., Pacot C., Dugail I., Lemarchand P., Guichard C., Le Liepvre X., Berthelier-Lubrano C., Spiegelman B., Kim J. B., Ferre P., and Foufelle F.. 1999. ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. Mol. Cell. Biol. 19:3760–3768.
  • Forman, B. M., Tontonoz P., Chen J., Brun R. P., Spiegelman B. M., and Evans R. M.. 1995. 15-Deoxy-delta 12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83:803–812.
  • Freytag, S. O., Paielli D. L., and Gilbert J. D.. 1994. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells. Genes Dev. 8:1654–1663.
  • Grefhorst, A., Elzinga B. M., Voshol P. J., Plosch T., Kok T., Bloks V. W., van der Sluijs F. H., Havekes L. M., Romijn J. A., Verkade H. J., and Kuipers F.. 2002. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J. Biol. Chem. 277:34182–34190.
  • Horton, J. D., Bashmakov Y., Shimomura I., and Shimano H.. 1998. Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Proc. Natl. Acad. Sci. USA 95:5987–5992.
  • Janowski, B. A., Willy P. J., Devi T. R., Falck J. R., and Mangelsdorf D. J.. 1996. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383:728–731.
  • Joseph, S. B., Laffitte B. A., Patel P. H., Watson M. A., Matsukuma K. E., Walczak R., Collins J. L., Osborne T. F., and Tontonoz P.. 2002. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J. Biol. Chem. 277:11019–11025.
  • Juvet, L. K., Andresen S. M., Schuster G. U., Dalen K. T., Tobin K. A., Hollung K., Haugen F., Jacinto S., Ulven S. M., Bamberg K., Gustafsson J.-Å., and Nebb H. I.. 2003. On the role of liver X receptors in lipid accumulation in adipocytes. Mol. Endocrinol. 17:172–182.
  • Kim, J. B., Sarraf P., Wright M., Yao K. M., Mueller E., Solanes G., Lowell B. B., and Spiegelman B. M.. 1998. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J. Clin. Investig. 101:1–9.
  • Kim, J. B., and Spiegelman B. M.. 1996. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 10:1096–1107.
  • Kim, J. B., Wright H. M., Wright M., and Spiegelman B. M.. 1998. ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc. Natl. Acad. Sci. USA 95:4333–4337.
  • Kim, S. W., Park K., Kwak E., Choi E., Lee S., Ham J., Kang H., Kim J. M., Hwang S. Y., Kong Y. Y., Lee K., and Lee J. W.. 2003. Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice. Mol. Cell. Biol. 23:3583–3592.
  • Kliewer, S. A., Lenhard J. M., Willson T. M., Patel I., Morris D. C., and Lehmann J. M.. 1995. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83:813–819.
  • Kubota, N., Terauchi Y., Miki H., Tamemoto H., Yamauchi T., Komeda K., Satoh S., Nakano R., Ishii C., Sugiyama T., Eto K., Tsubamoto Y., Okuno A., Murakami K., Sekihara H., Hasegawa G., Naito M., Toyoshima Y., Tanaka S., Shiota K., Kitamura T., Fujita T., Ezaki O., Aizawa S., Kadowaki T., et al. 1999. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell 4:597–609.
  • Laffitte, B. A., Repa J. J., Joseph S. B., Wilpitz D. C., Kast H. R., Mangelsdorf D. J., and Tontonoz P.. 2001. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc. Natl. Acad. Sci. USA 98:507–512.
  • Lehmann, J. M., Kliewer S. A., Moore L. B., Smith-Oliver T. A., Oliver B. B., Su J. L., Sundseth S. S., Winegar D. A., Blanchard D. E., Spencer T. A., and Willson T. M.. 1997. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J. Biol. Chem. 272:3137–3140.
  • Lehmann, J. M., Moore L. B., Smith-Oliver T. A., Wilkison W. O., Willson T. M., and Kliewer S. A.. 1995. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J. Biol. Chem. 270:12953–12956.
  • Liang, G., Yang J., Horton J. D., Hammer R. E., Goldstein J. L., and Brown M. S.. 2002. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J. Biol. Chem. 277:9520–9528.
  • Lin, F. T., and Lane M. D.. 1992. Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes. Genes Dev. 6:533–544.
  • Lin, F. T., and Lane M. D.. 1994. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. Proc. Natl. Acad. Sci. USA 91:8757–8761.
  • Lu, T. T., Repa J. J., and Mangelsdorf D. J.. 2001. Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism. J. Biol. Chem. 276:37735–37738.
  • Mohamed-Ali, V., J. H. Pinkney, and S. W. Coppack. 1998. Adipose tissue as an endocrine and paracrine organ. Int. J. Obes. Relat. Metab. Disord. 22:1145–1158.
  • Nadler, S. T., and Attie A. D.. 2001. Please pass the chips: genomic insights into obesity and diabetes. J. Nutr. 131:2078–2081.
  • Ou, J., Tu H., Shan B., Luk A., DeBose-Boyd R. A., Bashmakov Y., Goldstein J. L., and Brown M. S.. 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. Proc. Natl. Acad. Sci. USA 98:6027–6032.
  • Pawar, A., Xu J., Jerks E., Mangelsdorf D. J., and Jump D. B.. 2002. Fatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha) in HEK293 cells. J. Biol. Chem. 277:39243–39250.
  • Peet, D. J., Janowski B. A., and Mangelsdorf D. J.. 1998. The LXRs: a new class of oxysterol receptors. Curr. Opin. Genet. Dev. 8:571–575.
  • Peet, D. J., Turley S. D., Ma W., Janowski B. A., Lobaccaro J. M., Hammer R. E., and Mangelsdorf D. J.. 1998. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 93:693–704.
  • Plosch, T., Kok T., Bloks V. W., Smit M. J., Havinga R., Chimini G., Groen A. K., and Kuipers F.. 2002. Increased hepatobiliary and fecal cholesterol excretion upon activation of the liver X receptor is independent of ABCA1. J. Biol. Chem. 277:33870–33877.
  • Repa, J. J., Liang G., Ou J., Bashmakov Y., Lobaccaro J. M., Shimomura I., Shan B., Brown M. S., Goldstein J. L., and Mangelsdorf D. J.. 2000. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 14:2819–2830.
  • Repa, J. J., and Mangelsdorf D. J.. 2000. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu. Rev. Cell Dev. Biol. 16:459–481.
  • Rosen, E. D., Sarraf P., Troy A. E., Bradwin G., Moore K., Milstone D. S., Spiegelman B. M., and Mortensen R. M.. 1999. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4:611–617.
  • Rosen, E. D., Walkey C. J., Puigserver P., and Spiegelman B. M.. 2000. Transcriptional regulation of adipogenesis. Genes Dev. 14:1293–1307.
  • Ross, S. E., Erickson R. L., Gerin I., DeRose P. M., Bajnok L., Longo K. A., Misek D. E., Kuick R., Hanash S. M., Atkins K. B., Andresen S. M., Nebb H. I., Madsen L., Kristiansen K., and MacDougald O. A.. 2002. Microarray analyses during adipogenesis: understanding the effects of Wnt signaling on adipogenesis and the roles of liver X receptor α in adipocyte metabolism. Mol. Cell. Biol. 22:5989–5999.
  • Russell, D. W. 1999. Nuclear orphan receptors control cholesterol catabolism. Cell 97:539–542.
  • Saltiel, A. R. 2001. You are what you secrete. Nat. Med. 7:887–888.
  • Schultz, J. R., Tu H., Luk A., Repa J. J., Medina J. C., Li L., Schwendner S., Wang S., Thoolen M., Mangelsdorf D. J., Lustig K. D., and Shan B.. 2000. Role of LXRs in control of lipogenesis. Genes Dev. 14:2831–2838.
  • Shimano, H., Yahagi N., Amemiya-Kudo M., Hasty A. H., Osuga J., Tamura Y., Shionoiri F., Iizuka Y., Ohashi K., Harada K., Gotoda T., Ishibashi S., and Yamada N.. 1999. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J. Biol. Chem. 274:35832–35839.
  • Song, C., Kokontis J. M., Hiipakka R. A., and Liao S.. 1994. Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors. Proc. Natl. Acad. Sci. USA 91:10809–10813.
  • Sparrow, C. P., Baffic J., Lam M. H., Lund E. G., Adams A. D., Fu X., Hayes N., Jones A. B., Macnaul K. L., Ondeyka J., Singh S., Wang J., Zhou G., Moller D. E., Wright S. D., and Menke J. G.. 2002. A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux. J. Biol. Chem. 277:10021–10027.
  • Spiegelman, B. M., and Flier J. S.. 1996. Adipogenesis and obesity: rounding out the big picture. Cell 87:377–389.
  • Stern, M. P. 1995. Diabetes and cardiovascular disease. The “common soil” hypothesis. Diabetes 44:369–374.
  • Stulnig, T. M., Steffensen K. R., Gao H., Reimers M., Dahlman-Wright K., Schuster G. U., and Gustafsson J.-Å.. 2002. Novel roles of liver X receptors exposed by gene expression profiling in liver and adipose tissue. Mol. Pharmacol. 62:1299–1305.
  • Tabor, D. E., Kim J. B., Spiegelman B. M., and Edwards P. A.. 1999. Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2. J. Biol. Chem. 274:20603–20610.
  • Teboul, M., Enmark E., Li Q., Wikstrom A. C., Pelto-Huikko M., and Gustafsson J.-Å.. 1995. OR-1, a member of the nuclear receptor superfamily that interacts with the 9-cis-retinoic acid receptor. Proc. Natl. Acad. Sci. USA 92:2096–2100.
  • Tobin, K. A., Steineger H. H., Alberti S., Spydevold O., Auwerx J., Gustafsson J.-Å., and Nebb H. I.. 2000. Cross-talk between fatty acid and cholesterol metabolism mediated by liver X receptor-alpha. Mol. Endocrinol. 14:741–752.
  • Tontonoz, P., Hu E., Graves R. A., Budavari A. I., and Spiegelman B. M.. 1994. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 8:1224–1234.
  • Tontonoz, P., Hu E., and Spiegelman B. M.. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147–1156.
  • Tontonoz, P., Kim J. B., Graves R. A., and Spiegelman B. M.. 1993. ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Mol. Cell. Biol. 13:4753–4759.
  • Tontonoz, P., and Mangelsdorf D. J.. 2003. Liver X receptor signaling pathways in cardiovascular disease. Mol. Endocrinol. 17:985–993.
  • Venkateswaran, A., Laffitte B. A., Joseph S. B., Mak P. A., Wilpitz D. C., Edwards P. A., and Tontonoz P.. 2000. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc. Natl. Acad. Sci. USA 97:12097–12102.
  • Venkateswaran, A., Repa J. J., Lobaccaro J. M., Bronson A., Mangelsdorf D. J., and Edwards P. A.. 2000. Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A transcriptional role for specific oxysterols. J. Biol. Chem. 275:14700–14707.
  • Wiebel, F. F., and Gustafsson J.-Å.. 1997. Heterodimeric interaction between retinoid X receptor alpha and orphan nuclear receptor OR1 reveals dimerization-induced activation as a novel mechanism of nuclear receptor activation. Mol. Cell. Biol. 17:3977–3986.
  • Willy, P. J., and Mangelsdorf D. J.. 1997. Unique requirements for retinoid-dependent transcriptional activation by the orphan receptor LXR. Genes Dev. 11:289–298.
  • Willy, P. J., Umesono K., Ong E. S., Evans R. M., Heyman R. A., and Mangelsdorf D. J.. 1995. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 9:1033–1045.
  • Wu, Z., Puigserver P., and Spiegelman B. M.. 1999. Transcriptional activation of adipogenesis. Curr. Opin. Cell Biol. 11:689–694.
  • Wu, Z., Xie Y., Bucher N. L., and Farmer S. R.. 1995. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev. 9:2350–2363.
  • Yeh, W. C., Cao Z., Classon M., and McKnight S. L.. 1995. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 9:168–181.
  • Yoshikawa, T., Shimano H., Amemiya-Kudo M., Yahagi N., Hasty A. H., Matsuzaka T., Okazaki H., Tamura Y., Iizuka Y., Ohashi K., Osuga J., Harada K., Gotoda T., Kimura S., Ishibashi S., and Yamada N.. 2001. Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter. Mol. Cell. Biol. 21:2991–3000.
  • Zhang, Y., Repa J. J., Gauthier K., and Mangelsdorf D. J.. 2001. Regulation of lipoprotein lipase by the oxysterol receptors, LXRalpha and LXRbeta. J. Biol. Chem. 276:43018–43024.

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