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The NR4A family of orphan nuclear receptors are not required for adipogenesis

International Journal of Obesity volume 32, pages 388–392 (2008)Cite this article

Abstract

Nuclear hormone receptors of the NR4A subfamily are rapidly induced during the early stages of adipogenesis, leading to the speculation that they may have important roles in this process. One of the three subfamily members, Nur77 has also been shown to play key roles in energy expenditure and lipolysis in skeletal muscle and in the control of hepatic gluconeogenesis. We, therefore, examined the role of NR4A factors in adipogenesis using the well-characterized 3T3-L1 preadipocyte model. Inhibition of Nur77 expression using siRNA did not affect induction of adipogenic genes, nor the accumulation of lipid. To inhibit the activity of all the three NR4A family members, we generated preadipocytes stably expressing a well-characterized dominant-negative Nur77 (DN-Nur77), known to block the function of the other NR4A factors, Nurr1 and Nor1, as well as Nur77. While the increased NR4A activity observed following adipogenic induction was completely abolished in these cells, DN-Nur77 expression did not affect the expression of genes characteristic of terminally differentiated adipocytes and had no impact on lipid accumulation in these cells. Thus, while members of the NR4A subfamily of nuclear receptors may have important metabolic roles in skeletal muscle and liver, we demonstrate that they are dispensable for normal adipocyte development.

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References

  1. Crowley VE, Yeo GS, O'Rahilly S . Obesity therapy: altering the energy intake-and-expenditure balance sheet. Nat Rev Drug Discov 2002; 1: 276–286.

    Article  CAS  PubMed  Google Scholar 

  2. Hill JO, Wyatt HR, Reed GW, Peters JC . Obesity and the environment: where do we go from here? Science 2003; 299: 853–855.

    Article  CAS  PubMed  Google Scholar 

  3. Kahn BB, Flier JS . Obesity and insulin resistance. J Clin Invest 2000; 106: 473–481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kopelman PG . Obesity as a medical problem. Nature 2000; 404: 635–643.

    Article  CAS  PubMed  Google Scholar 

  5. Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ . The biology of white adipocyte proliferation. Obes Rev 2001; 2: 239–254.

    Article  CAS  PubMed  Google Scholar 

  6. Prins JB, O'Rahilly S . Regulation of adipose cell number in man. Clin Sci (London) 1997; 92: 3–11.

    Article  CAS  Google Scholar 

  7. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM . Transcriptional regulation of adipogenesis. Genes Dev 2000; 14: 1293–1307.

    CAS  PubMed  Google Scholar 

  8. Lin FT, Lane MD . CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. Proc Natl Acad Sci USA 1994; 91: 8757–8761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tontonoz P, Hu E, Spiegelman BM . Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994; 79: 1147–1156.

    Article  CAS  PubMed  Google Scholar 

  10. Rosen ED, MacDougald OA . Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 2006; 7: 885–896.

    Article  CAS  PubMed  Google Scholar 

  11. Fu M, Sun T, Bookout AL, Downes M, Yu RT, Evans RM et al. A nuclear receptor atlas: 3T3-L1 adipogenesis. Mol Endocrinol 2005; 19: 2437–2450.

    Article  CAS  PubMed  Google Scholar 

  12. Soukas A, Socci ND, Saatkamp BD, Novelli S, Friedman JM . Distinct transcriptional profiles of adipogenesis in vivo and in vitro. J Biol Chem 2001; 276: 34167–34174.

    Article  CAS  PubMed  Google Scholar 

  13. Maxwell MA, Cleasby ME, Harding A, Stark A, Cooney GJ, Muscat GE . Nur77 regulates lipolysis in skeletal muscle cells. Evidence for cross-talk between the beta-adrenergic and an orphan nuclear hormone receptor pathway. J Biol Chem 2005; 280: 12573–12584.

    Article  CAS  PubMed  Google Scholar 

  14. Pei L, Waki H, Vaitheesvaran B, Wilpitz DC, Kurland IJ, Tontonoz P . NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism. Nat Med 2006; 12: 1048–1055.

    Article  CAS  PubMed  Google Scholar 

  15. Rochford JJ, Semple RK, Laudes M, Boyle KB, Christodoulides C, Mulligan C et al. ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis. Mol Cell Biol 2004; 24: 9863–9872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cheng LE, Chan FK, Cado D, Winoto A . Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J 1997; 16: 1865–1875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Maira M, Martens C, Philips A, Drouin J . Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation. Mol Cell Biol 1999; 19: 7549–7557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Woronicz JD, Calnan B, Ngo V, Winoto A . Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature 1994; 367: 277–281.

    Article  CAS  PubMed  Google Scholar 

  19. Philips A, Lesage S, Gingras R, Maira MH, Gauthier Y, Hugo P et al. Novel dimeric Nur77 signaling mechanism in endocrine and lymphoid cells. Mol Cell Biol 1997; 17: 5946–5951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fumoto T, Yamaguchi T, Hirose F, Osumi T . Orphan nuclear receptor Nur77 accelerates the initial phase of adipocyte differentiation in 3T3-L1 cells by promoting mitotic clonal expansion. J Biochem (Tokyo) 2007; 141: 181–192.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the British Heart Foundation (JJR), Wellcome Trust (VAP, SOR) and The Dorothy Hodgkin Postgraduate Award Scheme (W-SA). JJR and SOR are members of the EUGENE2 consortium.

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  1. Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

    W-S Au, V A Payne, S O'Rahilly & J J Rochford

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  1. W-S Au
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  2. V A Payne
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  3. S O'Rahilly
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Correspondence to J J Rochford.

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Au, WS., Payne, V., O'Rahilly, S. et al. The NR4A family of orphan nuclear receptors are not required for adipogenesis. Int J Obes 32, 388–392 (2008). https://doi.org/10.1038/sj.ijo.0803763

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