GPR180, a component of TGFß signalling, promotes thermogenic adipocyte function by mediating CTHRC1 effects

The TGFß signalling pathway regulates diverse physiological processes such as cellular proliferation, differentiation, and growth. Based on the contradictory nature of the pathway, since both inhibition and overactivation cause severe diseases, moderate stimulation is essential to maintain homeostasis. Here, we identify CTHRC1/GPR180 as novel components, which represent an alternative axis, which mediates a low-grade activation of the TGFß signalling pathway. We demonstrate that chronic low-grade activation of this pathway via CTHRC1/GPR180 leads to an induction of brown adipocyte function in vitro and attenuates the development of obesity and hyperglycemia.