The adipocyte clock controls brown adipogenesis through the TGF-β and BMP signaling pathways

Journal of Cell Science
Deokhwa NamKe Ma

Abstract

The molecular clock is intimately linked to metabolic regulation, and brown adipose tissue plays a key role in energy homeostasis. However, whether the cell-intrinsic clock machinery participates in brown adipocyte development is unknown. Here, we show that Bmal1 (also known as ARNTL), the essential clock transcription activator, inhibits brown adipogenesis to adversely affect brown fat formation and thermogenic capacity. Global ablation of Bmal1 in mice increases brown fat mass and cold tolerance, and adipocyte-selective inactivation of Bmal1 recapitulates these effects and demonstrates its cell-autonomous role in brown adipocyte formation. Further loss- and gain-of-function studies in mesenchymal precursors and committed brown progenitors reveal that Bmal1 inhibits brown adipocyte lineage commitment and terminal differentiation. Mechanistically, Bmal1 inhibits brown adipogenesis through direct transcriptional control of key components of the TGF-β pathway together with reciprocally altered BMP signaling; activation of TGF-β or blockade of BMP pathways suppresses enhanced differentiation in Bmal1-deficient brown adipocytes. Collectively, our study demonstrates a novel temporal regulatory mechanism in fine-tuning brown adipocyt...Continue Reading

References

Apr 25, 2000·The EMBO Journal·J Massagué, D Wotton
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·W WangK Luo
Aug 29, 2002·Nature·Steven M Reppert, David R Weaver
Dec 9, 2003·Proceedings of the National Academy of Sciences of the United States of America·Weimin HeRonald M Evans
Jan 13, 2004·Physiological Reviews·Barbara Cannon, Jan Nedergaard
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·James A TimmonsBarbara Cannon
Oct 25, 2007·Cell·Stephane GestaC Ronald Kahn
Aug 23, 2008·Nature·Patrick SealeBruce M Spiegelman
Sep 9, 2008·Cell·Carla B GreenJoseph Bass
Apr 10, 2009·The New England Journal of Medicine·Wouter D van Marken LichtenbeltG J Jaap Teule
Apr 10, 2009·The New England Journal of Medicine·Aaron M CypessC Ronald Kahn
Apr 10, 2009·The New England Journal of Medicine·Kirsi A VirtanenPirjo Nuutila
Apr 9, 2010·Cell Metabolism·Jan Nedergaard, Barbara Cannon
Dec 4, 2010·Science·Joseph Bass, Joseph S Takahashi
Jul 5, 2011·Cell Metabolism·Hariom YadavSushil G Rane
Oct 11, 2011·Cell Metabolism·Dyan SellayahDevanjan Sikder
Nov 15, 2011·Nature·Peggy JanichSalvador Aznar Benitah
Nov 19, 2011·The International Journal of Biochemistry & Cell Biology·Won Kon KimSang Chul Lee
Dec 16, 2011·Trends in Endocrinology and Metabolism : TEM·Saurabh Sahar, Paolo Sassone-Corsi
Mar 3, 2012·Biochemical and Biophysical Research Communications·Fuyuki SatoHiroshi Kijima
May 15, 2012·Current Biology : CB·Till RoennebergCéline Vetter
May 23, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bingyan GuoKe Ma
Feb 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shu-Wen QianQi-Qun Tang
Mar 26, 2013·Journal of Cell Science·Somik ChatterjeeKe Ma
Apr 16, 2013·Cell Reports·Phillip KarpowiczNorbert Perrimon
Sep 21, 2013·Molecular Metabolism·Sylvie ChappuisUrs Albrecht
Oct 29, 2013·Nature·Zachary Gerhart-HinesMitchell A Lazar
Jan 21, 2014·Biomaterials·Mario Meng-Chiang KuoDong Kun Lee
Feb 8, 2014·Seminars in Cell & Developmental Biology·Tessa Gaarenstroom, Caroline S Hill
Jun 6, 2014·Nature·Vivian PeirceAntonio Vidal-Puig

❮ Previous
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Citations

Sep 22, 2015·International Journal of Molecular Sciences·Jung-Chun Lin
Feb 19, 2016·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Ippei ShimizuTohru Minamino
Oct 7, 2015·Frontiers in Endocrinology·Xiaoyong Yang, Hai-Bin Ruan
Sep 4, 2015·Diabetes, Obesity & Metabolism·Z Gerhart-Hines, M A Lazar
Mar 28, 2017·Experimental Cell Research·Stine Ninel HansenZachary Gerhart-Hines
Dec 1, 2017·International Journal of Molecular Sciences·Alexandre ValléeJean-Noël Vallée
Oct 6, 2019·Cellular and Molecular Life Sciences : CMLS·Kathyani Parasram, Phillip Karpowicz
Jun 4, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Takao HiraiMakoto Inoue
Jun 3, 2016·Cold Spring Harbor Perspectives in Biology·Takenobu Katagiri, Tetsuro Watabe
Mar 27, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hongshan YinKe Ma
Apr 2, 2020·Nature Chemical Biology·Simon MillerTsuyoshi Hirota
Mar 16, 2019·Scientific Reports·Somik ChatterjeeKe Ma
Mar 27, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Zhuang QianShufang Wu
Apr 8, 2020·Cells·Kristin Eckel-MahanMikhail G Kolonin
Sep 13, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Isaac K SundarIrfan Rahman
Sep 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiaopeng SongLi Gao
Dec 8, 2020·Molecular and Cellular Endocrinology·Xuekai XiongKe Ma
Jan 17, 2021·Experimental Gerontology·Zhuoying ChenXiangjie Liu
Aug 20, 2019·Trends in Cancer·Gabriele SulliSatchidananda Panda
Jul 1, 2020·Molecular and Cellular Endocrinology·Ruya LiuKe Ma
May 3, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Maaike E StraatSander Kooijman
Oct 10, 2021·Journal of Bone and Mineral Metabolism·Qian LiangChengming Zhu
Oct 30, 2021·Frontiers in Immunology·Elizabeth Olmsted-DavisAlan R Davis

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