GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1
Niemi Tarja; Amri Ez-Zoubir; Moser Caroline; Ding Lianggong; Neubauer Heike; Nuutila Pirjo; Dong Hua; Balazova Lucia; Ghoshdastider Umesh; Efthymiou Vissarion; Lamla Thorsten; Horváth Áron; Kiehlmann Elke; Horvath Carla; Wolfrum Christian; Virtanen Kirsi A.; Balaz Miroslav; Pelczar Pawel; Ukropec Josef; Kovanicova Zuzana; Ukropcova Barbara; Hamilton Bradford; Sun Wenfei; Ghosh Adhideb
GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1
Niemi Tarja
Amri Ez-Zoubir
Moser Caroline
Ding Lianggong
Neubauer Heike
Nuutila Pirjo
Dong Hua
Balazova Lucia
Ghoshdastider Umesh
Efthymiou Vissarion
Lamla Thorsten
Horváth Áron
Kiehlmann Elke
Horvath Carla
Wolfrum Christian
Virtanen Kirsi A.
Balaz Miroslav
Pelczar Pawel
Ukropec Josef
Kovanicova Zuzana
Ukropcova Barbara
Hamilton Bradford
Sun Wenfei
Ghosh Adhideb
NATURE PORTFOLIO
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2022012710841
https://urn.fi/URN:NBN:fi-fe2022012710841
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]