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. 1996 Apr;16(4):1567–1575. doi: 10.1128/mcb.16.4.1567

Distinct stages in adipogenesis revealed by retinoid inhibition of differentiation after induction of PPARgamma.

J C Xue 1, E J Schwarz 1, A Chawla 1, M A Lazar 1
PMCID: PMC231142  PMID: 8657131

Abstract

Retinoic acid (RA) inhibits adipocyte differentiation of 3T3-L1 preadipocytes but is effective only early in adipogenesis. RA prevented induction of the adipogenic factors PPARgamma and C/EBPalpha. Using receptor-specific ligands, we determined that the effects of RA were mediated by liganded RA receptors (RARs) rather than retinoid X receptors. Preadipocytes expressed primarily RARalpha and RARgamma; during adipocyte differentiation, RARalpha gene expression was nearly constant, whereas RARgamma1 mRNA and protein levels dramatically decreased. Ectopic expression of RARgamma1 extended the period of effectiveness of RA by 24 to 48h; RARalpha expression had a similar effect, suggesting functional redundancy of RAR subtypes. Remarkably, RA inhibited differentiation when added after PPARgamma1 and PPARgamma2 proteins had already been expressed and resulted in the loss of PPARgamma proteins from cells. By 72 to 96 h after the induction of differentiation, RA failed to prevent differentiation of even ectopic-RAR-expressing cells. Thus, the unresponsiveness of 3T3-L1 preadipocytes to RA after the induction of differentiation is initially due to the reduction in cellular RAR concentration rather than to the induction of PPARgamma. At later times cells continue along the differentiation pathway in a manner which is RA and RAR independent.

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Selected References

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  1. Allegretto E. A., Shevde N., Zou A., Howell S. R., Boehm M. F., Hollis B. W., Pike J. W. Retinoid X receptor acts as a hormone receptor in vivo to induce a key metabolic enzyme for 1,25-dihydroxyvitamin D3. J Biol Chem. 1995 Oct 13;270(41):23906–23909. doi: 10.1074/jbc.270.41.23906. [DOI] [PubMed] [Google Scholar]
  2. Apfel C., Bauer F., Crettaz M., Forni L., Kamber M., Kaufmann F., LeMotte P., Pirson W., Klaus M. A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7129–7133. doi: 10.1073/pnas.89.15.7129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barettino D., Vivanco Ruiz M. M., Stunnenberg H. G. Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor. EMBO J. 1994 Jul 1;13(13):3039–3049. doi: 10.1002/j.1460-2075.1994.tb06603.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boylan J. F., Lohnes D., Taneja R., Chambon P., Gudas L. J. Loss of retinoic acid receptor gamma function in F9 cells by gene disruption results in aberrant Hoxa-1 expression and differentiation upon retinoic acid treatment. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9601–9605. doi: 10.1073/pnas.90.20.9601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cao Z., Umek R. M., McKnight S. L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 Sep;5(9):1538–1552. doi: 10.1101/gad.5.9.1538. [DOI] [PubMed] [Google Scholar]
  6. Cavaillès V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P. J., Parker M. G. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 1995 Aug 1;14(15):3741–3751. doi: 10.1002/j.1460-2075.1995.tb00044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chawla A., Lazar M. A. Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha-thyroid hormone receptor gene, during adipocyte differentiation. J Biol Chem. 1993 Aug 5;268(22):16265–16269. [PubMed] [Google Scholar]
  8. Chawla A., Schwarz E. J., Dimaculangan D. D., Lazar M. A. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology. 1994 Aug;135(2):798–800. doi: 10.1210/endo.135.2.8033830. [DOI] [PubMed] [Google Scholar]
  9. Chen F., Law S. W., O'Malley B. W. Identification of two mPPAR related receptors and evidence for the existence of five subfamily members. Biochem Biophys Res Commun. 1993 Oct 29;196(2):671–677. doi: 10.1006/bbrc.1993.2302. [DOI] [PubMed] [Google Scholar]
  10. Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
  11. Christy R. J., Kaestner K. H., Geiman D. E., Lane M. D. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2593–2597. doi: 10.1073/pnas.88.6.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Christy R. J., Yang V. W., Ntambi J. M., Geiman D. E., Landschulz W. H., Friedman A. D., Nakabeppu Y., Kelly T. J., Lane M. D. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev. 1989 Sep;3(9):1323–1335. doi: 10.1101/gad.3.9.1323. [DOI] [PubMed] [Google Scholar]
  13. Davis K. D., Berrodin T. J., Stelmach J. E., Winkler J. D., Lazar M. A. Endogenous retinoid X receptors can function as hormone receptors in pituitary cells. Mol Cell Biol. 1994 Nov;14(11):7105–7110. doi: 10.1128/mcb.14.11.7105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dey A., Minucci S., Ozato K. Ligand-dependent occupancy of the retinoic acid receptor beta 2 promoter in vivo. Mol Cell Biol. 1994 Dec;14(12):8191–8201. doi: 10.1128/mcb.14.12.8191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Distel R. J., Ro H. S., Rosen B. S., Groves D. L., Spiegelman B. M. Nucleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos. Cell. 1987 Jun 19;49(6):835–844. doi: 10.1016/0092-8674(87)90621-0. [DOI] [PubMed] [Google Scholar]
  16. Fawell S. E., Lees J. A., White R., Parker M. G. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell. 1990 Mar 23;60(6):953–962. doi: 10.1016/0092-8674(90)90343-d. [DOI] [PubMed] [Google Scholar]
  17. Forman B. M., Tontonoz P., Chen J., Brun R. P., Spiegelman B. M., Evans R. M. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell. 1995 Dec 1;83(5):803–812. doi: 10.1016/0092-8674(95)90193-0. [DOI] [PubMed] [Google Scholar]
  18. Forman B. M., Umesono K., Chen J., Evans R. M. Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell. 1995 May 19;81(4):541–550. doi: 10.1016/0092-8674(95)90075-6. [DOI] [PubMed] [Google Scholar]
  19. Gearing K. L., Göttlicher M., Teboul M., Widmark E., Gustafsson J. A. Interaction of the peroxisome-proliferator-activated receptor and retinoid X receptor. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1440–1444. doi: 10.1073/pnas.90.4.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Giguère V., Shago M., Zirngibl R., Tate P., Rossant J., Varmuza S. Identification of a novel isoform of the retinoic acid receptor gamma expressed in the mouse embryo. Mol Cell Biol. 1990 May;10(5):2335–2340. doi: 10.1128/mcb.10.5.2335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Green H., Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell. 1975 May;5(1):19–27. doi: 10.1016/0092-8674(75)90087-2. [DOI] [PubMed] [Google Scholar]
  22. Green H., Meuth M. An established pre-adipose cell line and its differentiation in culture. Cell. 1974 Oct;3(2):127–133. doi: 10.1016/0092-8674(74)90116-0. [DOI] [PubMed] [Google Scholar]
  23. Halachmi S., Marden E., Martin G., MacKay H., Abbondanza C., Brown M. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science. 1994 Jun 3;264(5164):1455–1458. doi: 10.1126/science.8197458. [DOI] [PubMed] [Google Scholar]
  24. Hu E., Tontonoz P., Spiegelman B. M. Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9856–9860. doi: 10.1073/pnas.92.21.9856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hörlein A. J., När A. M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C. K. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5;377(6548):397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
  26. Imakado S., Bickenbach J. R., Bundman D. S., Rothnagel J. A., Attar P. S., Wang X. J., Walczak V. R., Wisniewski S., Pote J., Gordon J. S. Targeting expression of a dominant-negative retinoic acid receptor mutant in the epidermis of transgenic mice results in loss of barrier function. Genes Dev. 1995 Feb 1;9(3):317–329. doi: 10.1101/gad.9.3.317. [DOI] [PubMed] [Google Scholar]
  27. Kamei Y., Kawada T., Kazuki R., Sugimoto E. Retinoic acid receptor gamma 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes. Biochem J. 1993 Aug 1;293(Pt 3):807–812. doi: 10.1042/bj2930807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kamei Y., Kawada T., Mizukami J., Sugimoto E. The prevention of adipose differentiation of 3T3-L1 cells caused by retinoic acid is elicited through retinoic acid receptor alpha. Life Sci. 1994;55(16):PL307–PL312. doi: 10.1016/0024-3205(94)90073-6. [DOI] [PubMed] [Google Scholar]
  29. Kastner P., Krust A., Mendelsohn C., Garnier J. M., Zelent A., Leroy P., Staub A., Chambon P. Murine isoforms of retinoic acid receptor gamma with specific patterns of expression. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2700–2704. doi: 10.1073/pnas.87.7.2700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Katz D., Lazar M. A. Dominant negative activity of an endogenous thyroid hormone receptor variant (alpha 2) is due to competition for binding sites on target genes. J Biol Chem. 1993 Oct 5;268(28):20904–20910. [PubMed] [Google Scholar]
  31. Keller H., Dreyer C., Medin J., Mahfoudi A., Ozato K., Wahli W. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2160–2164. doi: 10.1073/pnas.90.6.2160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kletzien R. F., Clarke S. D., Ulrich R. G. Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol Pharmacol. 1992 Feb;41(2):393–398. [PubMed] [Google Scholar]
  33. Kliewer S. A., Forman B. M., Blumberg B., Ong E. S., Borgmeyer U., Mangelsdorf D. J., Umesono K., Evans R. M. 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. doi: 10.1073/pnas.91.15.7355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kliewer S. A., Lenhard J. M., Willson T. M., Patel I., Morris D. C., Lehmann J. M. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell. 1995 Dec 1;83(5):813–819. doi: 10.1016/0092-8674(95)90194-9. [DOI] [PubMed] [Google Scholar]
  35. Kliewer S. A., Umesono K., Noonan D. J., Heyman R. A., Evans R. M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature. 1992 Aug 27;358(6389):771–774. doi: 10.1038/358771a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kuri-Harcuch W. Differentiation of 3T3-F442A cells into adipocytes is inhibited by retinoic acid. Differentiation. 1982;23(2):164–169. doi: 10.1111/j.1432-0436.1982.tb01279.x. [DOI] [PubMed] [Google Scholar]
  37. Kurokawa R., DiRenzo J., Boehm M., Sugarman J., Gloss B., Rosenfeld M. G., Heyman R. A., Glass C. K. Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding. Nature. 1994 Oct 6;371(6497):528–531. doi: 10.1038/371528a0. [DOI] [PubMed] [Google Scholar]
  38. Kurokawa R., Söderström M., Hörlein A., Halachmi S., Brown M., Rosenfeld M. G., Glass C. K. Polarity-specific activities of retinoic acid receptors determined by a co-repressor. Nature. 1995 Oct 5;377(6548):451–454. doi: 10.1038/377451a0. [DOI] [PubMed] [Google Scholar]
  39. Landau N. R., Littman D. R. Packaging system for rapid production of murine leukemia virus vectors with variable tropism. J Virol. 1992 Aug;66(8):5110–5113. doi: 10.1128/jvi.66.8.5110-5113.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Le Douarin B., Zechel C., Garnier J. M., Lutz Y., Tora L., Pierrat P., Heery D., Gronemeyer H., Chambon P., Losson R. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18. EMBO J. 1995 May 1;14(9):2020–2033. doi: 10.1002/j.1460-2075.1995.tb07194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lehmann J. M., Jong L., Fanjul A., Cameron J. F., Lu X. P., Haefner P., Dawson M. I., Pfahl M. Retinoids selective for retinoid X receptor response pathways. Science. 1992 Dec 18;258(5090):1944–1946. doi: 10.1126/science.1335166. [DOI] [PubMed] [Google Scholar]
  42. Lehmann J. M., Moore L. B., Smith-Oliver T. A., Wilkison W. O., Willson T. M., Kliewer S. A. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953–12956. doi: 10.1074/jbc.270.22.12953. [DOI] [PubMed] [Google Scholar]
  43. Leid M., Kastner P., Chambon P. Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci. 1992 Oct;17(10):427–433. doi: 10.1016/0968-0004(92)90014-z. [DOI] [PubMed] [Google Scholar]
  44. Lepar G. J., Jump D. B. Retinoic acid and dexamethasone interact to regulate S14 gene transcription in 3T3-F442A adipocytes. Mol Cell Endocrinol. 1992 Mar;84(1-2):65–72. doi: 10.1016/0303-7207(92)90072-e. [DOI] [PubMed] [Google Scholar]
  45. Li E., Sucov H. M., Lee K. F., Evans R. M., Jaenisch R. Normal development and growth of mice carrying a targeted disruption of the alpha 1 retinoic acid receptor gene. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1590–1594. doi: 10.1073/pnas.90.4.1590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Lin F. T., Lane M. D. Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes. Genes Dev. 1992 Apr;6(4):533–544. doi: 10.1101/gad.6.4.533. [DOI] [PubMed] [Google Scholar]
  47. Lin F. T., Lane M. D. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8757–8761. doi: 10.1073/pnas.91.19.8757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Lohnes D., Kastner P., Dierich A., Mark M., LeMeur M., Chambon P. Function of retinoic acid receptor gamma in the mouse. Cell. 1993 May 21;73(4):643–658. doi: 10.1016/0092-8674(93)90246-m. [DOI] [PubMed] [Google Scholar]
  49. Matsui T., Sashihara S. Tissue-specific distribution of a novel C-terminal truncation retinoic acid receptor mutant which acts as a negative repressor in a promoter- and cell-type-specific manner. Mol Cell Biol. 1995 Apr;15(4):1961–1967. doi: 10.1128/mcb.15.4.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Miller A. D., Rosman G. J. Improved retroviral vectors for gene transfer and expression. Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90. [PMC free article] [PubMed] [Google Scholar]
  51. Nagpal S., Saunders M., Kastner P., Durand B., Nakshatri H., Chambon P. Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors. Cell. 1992 Sep 18;70(6):1007–1019. doi: 10.1016/0092-8674(92)90250-g. [DOI] [PubMed] [Google Scholar]
  52. Perlmann T., Jansson L. A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev. 1995 Apr 1;9(7):769–782. doi: 10.1101/gad.9.7.769. [DOI] [PubMed] [Google Scholar]
  53. Ron D., Habener J. F. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 1992 Mar;6(3):439–453. doi: 10.1101/gad.6.3.439. [DOI] [PubMed] [Google Scholar]
  54. Sadowski H. B., Wheeler T. T., Young D. A. Gene expression during 3T3-L1 adipocyte differentiation. Characterization of initial responses to the inducing agents and changes during commitment to differentiation. J Biol Chem. 1992 Mar 5;267(7):4722–4731. [PubMed] [Google Scholar]
  55. Safonova I., Reichert U., Shroot B., Ailhaud G., Grimaldi P. Fatty acids and retinoids act synergistically on adipose cell differentiation. Biochem Biophys Res Commun. 1994 Oct 28;204(2):498–504. doi: 10.1006/bbrc.1994.2487. [DOI] [PubMed] [Google Scholar]
  56. Sato M., Hiragun A., Mitsui H. Preadipocytes possess cellular retinoid binding proteins and their differentiation is inhibited by retinoids. Biochem Biophys Res Commun. 1980 Aug 29;95(4):1839–1845. doi: 10.1016/s0006-291x(80)80113-6. [DOI] [PubMed] [Google Scholar]
  57. Spiegelman B. M., Frank M., Green H. Molecular cloning of mRNA from 3T3 adipocytes. Regulation of mRNA content for glycerophosphate dehydrogenase and other differentiation-dependent proteins during adipocyte development. J Biol Chem. 1983 Aug 25;258(16):10083–10089. [PubMed] [Google Scholar]
  58. Sporn M. B., Roberts A. B. Role of retinoids in differentiation and carcinogenesis. Cancer Res. 1983 Jul;43(7):3034–3040. [PubMed] [Google Scholar]
  59. Stone R. L., Bernlohr D. A. The molecular basis for inhibition of adipose conversion of murine 3T3-L1 cells by retinoic acid. Differentiation. 1990 Nov;45(2):119–127. doi: 10.1111/j.1432-0436.1990.tb00465.x. [DOI] [PubMed] [Google Scholar]
  60. Taneja R., Bouillet P., Boylan J. F., Gaub M. P., Roy B., Gudas L. J., Chambon P. Reexpression of retinoic acid receptor (RAR) gamma or overexpression of RAR alpha or RAR beta in RAR gamma-null F9 cells reveals a partial functional redundancy between the three RAR types. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7854–7858. doi: 10.1073/pnas.92.17.7854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tontonoz P., Hu E., Devine J., Beale E. G., Spiegelman B. M. PPAR gamma 2 regulates adipose expression of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1995 Jan;15(1):351–357. doi: 10.1128/mcb.15.1.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tontonoz P., Hu E., Graves R. A., Budavari A. I., Spiegelman B. M. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994 May 15;8(10):1224–1234. doi: 10.1101/gad.8.10.1224. [DOI] [PubMed] [Google Scholar]
  63. Tontonoz P., Hu E., Spiegelman B. M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994 Dec 30;79(7):1147–1156. doi: 10.1016/0092-8674(94)90006-x. [DOI] [PubMed] [Google Scholar]
  64. Tontonoz P., Kim J. B., Graves R. A., Spiegelman B. M. ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Mol Cell Biol. 1993 Aug;13(8):4753–4759. doi: 10.1128/mcb.13.8.4753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Umesono K., Murakami K. K., Thompson C. C., Evans R. M. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell. 1991 Jun 28;65(7):1255–1266. doi: 10.1016/0092-8674(91)90020-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Vasseur-Cognet M., Lane M. D. Trans-acting factors involved in adipogenic differentiation. Curr Opin Genet Dev. 1993 Apr;3(2):238–245. doi: 10.1016/0959-437x(93)90029-o. [DOI] [PubMed] [Google Scholar]
  67. Willy P. J., Umesono K., Ong E. S., Evans R. M., Heyman R. A., Mangelsdorf D. J. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 1995 May 1;9(9):1033–1045. doi: 10.1101/gad.9.9.1033. [DOI] [PubMed] [Google Scholar]
  68. Wu Z., Xie Y., Bucher N. L., Farmer S. R. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev. 1995 Oct 1;9(19):2350–2363. doi: 10.1101/gad.9.19.2350. [DOI] [PubMed] [Google Scholar]
  69. Yeh W. C., Cao Z., Classon M., McKnight S. L. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 1995 Jan 15;9(2):168–181. doi: 10.1101/gad.9.2.168. [DOI] [PubMed] [Google Scholar]
  70. Yu K., Bayona W., Kallen C. B., Harding H. P., Ravera C. P., McMahon G., Brown M., Lazar M. A. Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem. 1995 Oct 13;270(41):23975–23983. doi: 10.1074/jbc.270.41.23975. [DOI] [PubMed] [Google Scholar]
  71. Zhu Y., Qi C., Korenberg J. R., Chen X. N., Noya D., Rao M. S., Reddy J. K. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7921–7925. doi: 10.1073/pnas.92.17.7921. [DOI] [PMC free article] [PubMed] [Google Scholar]

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