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GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1

Author

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  • Lucia Balazova

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Miroslav Balaz

    (Institute of Food, Nutrition and Health, ETH Zürich
    Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences
    Comenius University in Bratislava)

  • Carla Horvath

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Áron Horváth

    (University Hospital Balgrist, University of Zurich
    Institute of Biomechanics, ETH Zurich)

  • Caroline Moser

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Zuzana Kovanicova

    (Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences)

  • Adhideb Ghosh

    (Institute of Food, Nutrition and Health, ETH Zürich
    Functional Genomics Centre Zurich, ETH Zurich/ University of Zurich)

  • Umesh Ghoshdastider

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Vissarion Efthymiou

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Elke Kiehlmann

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Wenfei Sun

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Hua Dong

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Lianggong Ding

    (Institute of Food, Nutrition and Health, ETH Zürich)

  • Ez-Zoubir Amri

    (Université Côte d’Azur, French National Centre for Scientific Research, Inserm, iBV)

  • Pirjo Nuutila

    (University of Turku)

  • Kirsi A. Virtanen

    (University of Turku)

  • Tarja Niemi

    (Turku University Hospital)

  • Barbara Ukropcova

    (Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences
    Institute of Pathophysiology, Faculty of Medicine, Comenius University)

  • Jozef Ukropec

    (Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences)

  • Pawel Pelczar

    (University of Basel)

  • Thorsten Lamla

    (Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG)

  • Bradford Hamilton

    (Cardiometabolic Diseases Research Department, Boehringer Ingelheim Pharma GmbH and Co. KG)

  • Heike Neubauer

    (Cardiometabolic Diseases Research Department, Boehringer Ingelheim Pharma GmbH and Co. KG)

  • Christian Wolfrum

    (Institute of Food, Nutrition and Health, ETH Zürich)

Abstract

Activation of thermogenic brown and beige adipocytes is considered as a strategy to improve metabolic control. Here, we identify GPR180 as a receptor regulating brown and beige adipocyte function and whole-body glucose homeostasis, whose expression in humans is associated with improved metabolic control. We demonstrate that GPR180 is not a GPCR but a component of the TGFβ signalling pathway and regulates the activity of the TGFβ receptor complex through SMAD3 phosphorylation. In addition, using genetic and pharmacological tools, we provide evidence that GPR180 is required to manifest Collagen triple helix repeat containing 1 (CTHRC1) action to regulate brown and beige adipocyte activity and glucose homeostasis. In this work, we show that CTHRC1/GPR180 signalling integrates into the TGFβ signalling as an alternative axis to fine-tune and achieve low-grade activation of the pathway to prevent pathophysiological response while contributing to control of glucose and energy metabolism.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27442-x
    DOI: 10.1038/s41467-021-27442-x
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