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The Gq signalling pathway inhibits brown and beige adipose tissue

Author

Listed:
  • Katarina Klepac

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
    Research Training Group 1873, University of Bonn)

  • Ana Kilić

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
    Research Training Group 1873, University of Bonn)

  • Thorsten Gnad

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn)

  • Loren M. Brown

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
    University of California)

  • Beate Herrmann

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
    Research Training Group 1873, University of Bonn)

  • Andrea Wilderman

    (University of California)

  • Aileen Balkow

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn)

  • Anja Glöde

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn)

  • Katharina Simon

    (Research Training Group 1873, University of Bonn
    Institute of Pharmaceutical Biology, University of Bonn)

  • Martin E. Lidell

    (Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg)

  • Matthias J. Betz

    (Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg)

  • Sven Enerbäck

    (Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg)

  • Jürgen Wess

    (Molecular Signalling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Marc Freichel

    (Institute of Pharmacology, University of Heidelberg)

  • Matthias Blüher

    (University of Leipzig)

  • Gabi König

    (Institute of Pharmaceutical Biology, University of Bonn)

  • Evi Kostenis

    (Research Training Group 1873, University of Bonn
    Institute of Pharmaceutical Biology, University of Bonn)

  • Paul A. Insel

    (University of California
    University of California)

  • Alexander Pfeifer

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
    Research Training Group 1873, University of Bonn
    PharmaCenter, University of Bonn)

Abstract

Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the Gq family, and inhibition of Gq signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of Gq signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of Gq signalling in brown adipocytes. Expression of a constitutively active Gq protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of Gq in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that Gq signalling regulates brown/beige adipocytes and inhibition of Gq signalling may be a novel therapeutic approach to combat obesity.

Suggested Citation

  • Katarina Klepac & Ana Kilić & Thorsten Gnad & Loren M. Brown & Beate Herrmann & Andrea Wilderman & Aileen Balkow & Anja Glöde & Katharina Simon & Martin E. Lidell & Matthias J. Betz & Sven Enerbäck & , 2016. "The Gq signalling pathway inhibits brown and beige adipose tissue," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10895
    DOI: 10.1038/ncomms10895
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    Cited by:

    1. Lucia Balazova & Miroslav Balaz & Carla Horvath & Áron Horváth & Caroline Moser & Zuzana Kovanicova & Adhideb Ghosh & Umesh Ghoshdastider & Vissarion Efthymiou & Elke Kiehlmann & Wenfei Sun & Hua Dong, 2021. "GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Tatsuya Yoshizawa & Yoshifumi Sato & Shihab U. Sobuz & Tomoya Mizumoto & Tomonori Tsuyama & Md. Fazlul Karim & Keishi Miyata & Masayoshi Tasaki & Masaya Yamazaki & Yuichi Kariba & Norie Araki & Eiichi, 2022. "SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Julian Brands & Sergi Bravo & Lars Jürgenliemke & Lukas Grätz & Hannes Schihada & Fabian Frechen & Judith Alenfelder & Cy Pfeil & Paul Georg Ohse & Suzune Hiratsuka & Kouki Kawakami & Luna C. Schmacke, 2024. "A molecular mechanism to diversify Ca2+ signaling downstream of Gs protein-coupled receptors," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. Takefumi Kimura & Sai P. Pydi & Lei Wang & Dhanush Haspula & Yinghong Cui & Huiyan Lu & Gabriele M. König & Evi Kostenis & Gregory R. Steinberg & Oksana Gavrilova & Jürgen Wess, 2022. "Adipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Chih-Hao Wang & Tadataka Tsuji & Li-Hong Wu & Cheng-Ying Yang & Tian Lian Huang & Mari Sato & Farnaz Shamsi & Yu-Hua Tseng, 2024. "Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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