GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1
: Balazova Lucia, Balaz Miroslav, Horvath Carla, Horváth Áron, Moser Caroline, Kovanicova Zuzana, Ghosh Adhideb, Ghoshdastider Umesh, Efthymiou Vissarion, Kiehlmann Elke, Sun Wenfei, Dong Hua, Ding Lianggong, Amri Ez-Zoubir, Nuutila Pirjo, Virtanen Kirsi A., Niemi Tarja, Ukropcova Barbara, Ukropec Josef, Pelczar Pawel, Lamla Thorsten, Hamilton Bradford, Neubauer Heike, Wolfrum Christian
Publisher: NATURE PORTFOLIO
: 2021
: Nature Communications
: NAT COMMUN
: ARTN 7144
: 12
: 1
: 18
: 2041-1723
DOI: https://doi.org/10.1038/s41467-021-27442-x
: https://www.nature.com/articles/s41467-021-27442-x
: https://research.utu.fi/converis/portal/detail/Publication/68372011
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 TGF beta signalling pathway and regulates the activity of the TGF beta 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 TGF beta 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.Activation of thermogenic adipocytes is a strategy to combat metabolic diseases. Here the authors report that GPR180 is a component of TGF beta signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1, and contributes to the regulation of glucose and energy metabolism.
