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BET bromodomain inhibition suppresses adipogenesis in mice

  • Qiong DuanEmail author
  • Pei Wu
  • Zhenzhen Liu
  • Fan Xia
  • Lingyan Zhu
  • Zeqi Zheng
  • Tianlun YangEmail author
  • Jun QiEmail author
Endocrine Genetics/Epigenetics



We recently reported that inhibition of BET bromodomain suppresses adipogenesis in vitro. In the present study we aimed to address whether BET bromodomain inhibition can suppress adipogenesis in vivo.


Brd4fl/fl mice were crossed with B6.Cg-Tg(Fabp4-cre)1Rev/J mice to generate Brd4fl/+/Fabp4-cre mice. We used high fat diet (HFD, 45% fat) mice treated with vehicle (DMSO) or JQ1 (intraperitoneal, IP injection, 50 mg/kg/day), respectively, for 6 weeks. Body weight was measured once a week. Dual-energy X-ray absorptiometry was determined and brown adipose tissue was harvested at the end of the experiment.


Partial deletion of Brd4 leads to the lower body weight. JQ1 treatment further confirmed that BET bromodomain inhibition suppresses body weight gain and decreases white adipose depots compared with the control mice. In addition, JQ1 treatment reduces the size of brown adipose tissue and impairs its thermogenesis.


BET bromodomain inhibition suppresses adipogenesis in the mice.


BET bromodomain Adipogenesis JQ1 Epigenetics 



We thank Xiong Xiao for assistance with image editing and Virangika K. Wimalasena for critical reading and editing of the paper. This work was supported by grants from the National Natural Science Foundation of China 81370320, 81770358, 81570334 (T.Y.), 81770867 (Q.D.), the National Institute of Health in US (NIH) HL-127240 (J.Q.), the Natural Science Foundation of Hunan Province 2017JJ2379 (Q.D.), China Postdoctoral Science Foundation 2017T100612 (Q.D.), and the Zijing Foundation 2014-0016 (Q.D.).

Author contributions

Q.D., P.W., Z.L., F.X., L.Z., performed the studies; Q.D., T.Y., and J.Q. designed the research, analyzed data, and prepared the paper; Q.D., T.Y., Z.Z., and J.Q. contributed to the discussion and supervised the study. All authors read and approved the final version of the paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

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Supplemental Figures Legends
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Supplemental Figure 1
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Supplemental Figure 2
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Supplemental Figure 3
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Supplemental Figure 4
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Supplemental Figure 5


  1. 1.
    E.D. Rosen, O.A. MacDougald, Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7, 885–896 (2006)CrossRefGoogle Scholar
  2. 2.
    J.D. Brown, Z.B. Feldman, S.P. Doherty, J.M. Reyes, P.B. Rahl, C.Y. Lin, Q. Sheng, Q. Duan, A.J. Federation, A.L. Kung, S.M. Haldar, R.A. Young, J. Plutzky, J.E. Bradner, BET bromodomain proteins regulate enhancer function during adipogenesis. Proc. Natl Acad. Sci. USA 115, 2144–2149 (2018)CrossRefGoogle Scholar
  3. 3.
    M.I. Lefterova, A.K. Haakonsson, M.A. Lazar, S. Mandrup, PPARgamma and the global map of adipogenesis and beyond. Trends Endocrinol. Metab. 25, 293–302 (2014)CrossRefGoogle Scholar
  4. 4.
    P. Filippakopoulos, J. Qi, S. Picaud, Y. Shen, W.B. Smith, O. Fedorov, E.M. Morse, T. Keates, T.T. Hickman, I. Felletar, M. Philpott, S. Munro, M.R. McKeown, Y. Wang, A.L. Christie, N. West, M.J. Cameron, B. Schwartz, T.D. Heightman, N. La Thangue, C.A. French, O. Wiest, A.L. Kung, S. Knapp, J.E. Bradner, Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010)CrossRefGoogle Scholar
  5. 5.
    E. Nicodeme, K.L. Jeffrey, U. Schaefer, S. Beinke, S. Dewell, C.W. Chung, R. Chandwani, I. Marazzi, P. Wilson, H. Coste, J. White, J. Kirilovsky, C.M. Rice, J.M. Lora, R.K. Prinjha, K. Lee, A. Tarakhovsky, Suppression of inflammation by a synthetic histone mimic. Nature 468, 1119–1123 (2010)CrossRefGoogle Scholar
  6. 6.
    J.E. Lee, Y.K. Park, S. Park, Y. Jang, N. Waring, A. Dey, K. Ozato, B. Lai, W. Peng, K. Ge, Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis. Nat. Commun. 8, 2217 (2017)CrossRefGoogle Scholar
  7. 7.
    X. Tang, R. Peng, J.E. Phillips, J. Deguzman, Y. Ren, S. Apparsundaram, Q. Luo, C.M. Bauer, M.E. Fuentes, J.A. DeMartino, G. Tyagi, R. Garrido, C.M. Hogaboam, C.P. Denton, A.M. Holmes, C. Kitson, C.S. Stevenson, D.C. Budd, Assessment of Brd4 inhibition in idiopathic pulmonary fibrosis lung fibroblasts and in vivo models of lung fibrosis. Am. J. Pathol. 183, 470–479 (2013)CrossRefGoogle Scholar
  8. 8.
    D. Houzelstein, S.L. Bullock, D.E. Lynch, E.F. Grigorieva, V.A. Wilson, R.S. Beddington, Growth and early postimplantation defects in mice deficient for the bromodomain-containing protein Brd4. Mol. Cell. Biol. 22, 3794–3802 (2002)CrossRefGoogle Scholar
  9. 9.
    M. Lopez, R. Lage, A.K. Saha, D. Perez-Tilve, M.J. Vazquez, L. Varela, S. Sangiao-Alvarellos, S. Tovar, K. Raghay, S. Rodriguez-Cuenca, R.M. Deoliveira, T. Castaneda, R. Datta, J.Z. Dong, M. Culler, M.W. Sleeman, C.V. Alvarez, R. Gallego, C.J. Lelliott, D. Carling, M.H. Tschop, C. Dieguez, A. Vidal-Puig, Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab. 7, 389–399 (2008)CrossRefGoogle Scholar
  10. 10.
    G.J. Morton, D.E. Cummings, D.G. Baskin, G.S. Barsh, M.W. Schwartz, Central nervous system control of food intake and body weight. Nature 443, 289–295 (2006)CrossRefGoogle Scholar
  11. 11.
    J.W. Park, K.H. Jung, J.H. Lee, C.H. Quach, S.H. Moon, Y.S. Cho, K.H. Lee, 18F-FDG PET/CT monitoring of beta3 agonist-stimulated brown adipocyte recruitment in white adipose tissue. J. Nucl. Med. 56, 153–158 (2015)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyThe First Affiliated Hospital of Nanchang UniversityNanchangChina
  2. 2.Jiangxi Hypertension Research InstituteNanchangChina
  3. 3.Department of Cardiology, Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.Department of EndocrinologyThe First Affiliated Hospital of Nanchang UniversityNanchangChina
  5. 5.Department of Cancer BiologyDana Farber Cancer InstituteBostonUSA
  6. 6.Department of MedicineHarvard Medical SchoolBostonUSA

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