Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Prdm4 induction by the small molecule butein promotes white adipose tissue browning

Abstract

Increasing the thermogenic activity of adipocytes holds promise as an approach to combating human obesity and related metabolic diseases. We identified induction of mouse PR domain containing 4 (Prdm4) by the small molecule butein as a means to induce expression of uncoupling protein 1 (Ucp1), increase energy expenditure, and stimulate the generation of thermogenic adipocytes. This study highlights a Prdm4-dependent pathway, modulated by small molecules, that stimulates browning of white adipose tissue.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Identification of Prdm4 as a butein-induced gene.
Figure 2: Prdm4 induces Ucp1 and regulates mitochondrial respiration.
Figure 3: Effects of Prdm4 knockdown in HFD induced obese mice.

Accession codes

Primary accessions

Gene Expression Omnibus

References

  1. Tontonoz, P. & Spiegelman, B.M. Annu. Rev. Biochem. 77, 289–312 (2008).

    Article  CAS  Google Scholar 

  2. Peirce, V., Carobbio, S. & Vidal-Puig, A. Nature 510, 76–83 (2014).

    Article  CAS  Google Scholar 

  3. Spiegelman, B.M. & Flier, J.S. Cell 104, 531–543 (2001).

    Article  CAS  Google Scholar 

  4. Cannon, B. & Nedergaard, J. Physiol. Rev. 84, 277–359 (2004).

    Article  CAS  Google Scholar 

  5. van Marken Lichtenbelt, W.D. et al. N. Engl. J. Med. 360, 1500–1508 (2009).

    Article  CAS  Google Scholar 

  6. Nedergaard, J., Bengtsson, T. & Cannon, B. Am. J. Physiol. Endocrinol. Metab. 293, E444–E452 (2007).

    Article  CAS  Google Scholar 

  7. Cypess, A.M. et al. N. Engl. J. Med. 360, 1509–1517 (2009).

    Article  CAS  Google Scholar 

  8. Virtanen, K.A. et al. N. Engl. J. Med. 360, 1518–1525 (2009).

    Article  CAS  Google Scholar 

  9. Wu, J. et al. Cell 150, 366–376 (2012).

    Article  CAS  Google Scholar 

  10. Rosenwald, M., Perdikari, A., Rülicke, T. & Wolfrum, C. Nat. Cell Biol. 15, 659–667 (2013).

    Article  CAS  Google Scholar 

  11. Seale, P. et al. Nature 454, 961–967 (2008).

    Article  CAS  Google Scholar 

  12. Timmons, J.A. et al. Proc. Natl. Acad. Sci. USA 104, 4401–4406 (2007).

    Article  CAS  Google Scholar 

  13. Cohen, P. et al. Cell 156, 304–316 (2014).

    Article  CAS  Google Scholar 

  14. Feldmann, H.M., Golozoubova, V., Cannon, B. & Nedergaard, J. Cell Metab. 9, 203–209 (2009).

    Article  CAS  Google Scholar 

  15. Ghorbani, M. & Himms-Hagen, J. Int. J. Obes. Relat. Metab. Disord. 21, 465–475 (1997).

    Article  CAS  Google Scholar 

  16. Barbatelli, G. et al. Am. J. Physiol. Endocrinol. Metab. 298, E1244–E1253 (2010).

    Article  CAS  Google Scholar 

  17. Harms, M.J. et al. Cell Metab. 19, 593–604 (2014).

    Article  CAS  Google Scholar 

  18. Roberts, L.D. et al. Cell Metab. 19, 96–108 (2014).

    Article  CAS  Google Scholar 

  19. Zhang, Z. et al. Nat. Commun. 5, 5493 (2014).

    Article  CAS  Google Scholar 

  20. van Dam, A.D. et al. Diabetes 64, 1544–1554 (2015).

    Article  CAS  Google Scholar 

  21. Song, N.J. et al. J. Lipid Res. 54, 1385–1396 (2013).

    Article  CAS  Google Scholar 

  22. Harms, M. & Seale, P. Nat. Med. 19, 1252–1263 (2013).

    Article  CAS  Google Scholar 

  23. Seale, P. Diabetes 64, 2369–2375 (2015).

    Article  CAS  Google Scholar 

  24. Wu, Z. & Wang, S. Dev. Biol. 373, 235–243 (2013).

    Article  CAS  Google Scholar 

  25. Seale, P. et al. Cell Metab. 6, 38–54 (2007).

    Article  CAS  Google Scholar 

  26. Park, K.W., Waki, H., Choi, S.P., Park, K.M. & Tontonoz, P. J. Lipid Res. 51, 2775–2784 (2010).

    Article  CAS  Google Scholar 

  27. Park, K.W. et al. Mol. Endocrinol. 22, 2038–2048 (2008).

    Article  CAS  Google Scholar 

  28. Kiefer, F.W. et al. Nat. Med. 18, 918–925 (2012).

    Article  CAS  Google Scholar 

  29. Samuel, V.T. et al. Diabetes 55, 2042–2050 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

T37i cells were kindly provided by M. Lombes. We thank T.H. Kwak for technical advice. This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (NRF-2013R1A1A2060447 to K.W.P.), and by the KRIBB Research Initiative Program (J.-S.L.). This study was also supported by the US National Institutes of Health (HL090553 to K.R. and F32 DK104484-01 to P.R.).

Author information

Authors and Affiliations

Authors

Contributions

K.W.P. and N.-J.S. designed the research; S.K., S.-H.C., and S.-M.K. performed parts of the animal experiments; P.R., L.V., and K.R. performed cellular energy expenditure analysis; S.C. and S.-H.K. performed in vivo metabolic studies; J.-M.K. assessed the purity of the compound; N.-J.S., P.R., P.T., L.V., J.-H.Y., J.-M.K., K.R., J.-S.L., S.L., S.-H.K., and K.W.P. were involved in data interpretation; K.W.P., N.-J.S., K.R., and P.T. wrote the manuscript.

Corresponding author

Correspondence to Kye Won Park.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results, Supplementary Table 1 and Supplementary Figures 1–22. (PDF 2139 kb)

Supplementary Note

Synthetic Procedures (PDF 83 kb)

Supplementary Data Set 1

Lists of butein selective genes (XLSX 18 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Song, NJ., Choi, S., Rajbhandari, P. et al. Prdm4 induction by the small molecule butein promotes white adipose tissue browning. Nat Chem Biol 12, 479–481 (2016). https://doi.org/10.1038/nchembio.2081

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.2081

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing