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


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.

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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.

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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.).

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Authors and Affiliations



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.

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Correspondence to Kye Won Park.

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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)

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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).

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