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

Lucia Balazova, Miroslav Balaz, Carla Horvath, Áron Horváth, Caroline Moser, Zuzana Kovanicova, Adhideb Ghosh, Umesh Ghoshdastider, Vissarion Efthymiou, Elke Kiehlmann, Wenfei Sun, Hua Dong, Lianggong Ding, Ez-Zoubir Amri, Pirjo Nuutila, Kirsi A. Virtanen, Tarja Niemi, Barbara Ukropcova, Jozef Ukropec, Pawel Pelczar, Thorsten Lamla, Bradford Hamilton, Heike Neubauer and Christian Wolfrum ()
Additional contact information
Lucia Balazova: Institute of Food, Nutrition and Health, ETH Zürich
Miroslav Balaz: Institute of Food, Nutrition and Health, ETH Zürich
Carla Horvath: Institute of Food, Nutrition and Health, ETH Zürich
Áron Horváth: University Hospital Balgrist, University of 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
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27442-x

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DOI: 10.1038/s41467-021-27442-x

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