Lack of adipocyte purinergic P2Y₆ receptor greatly improves whole body glucose homeostasis.

ABSTRACT: Uridine diphosphate (UDP)-activated purinergic receptor P2Y₆ (P2Y₆R) plays a crucial role in controlling energy balance through central mechanisms. However, P2Y₆R's roles in peripheral tissues regulating energy and glucose homeostasis remain unexplored. Here, we report the surprising finding that adipocyte-specific deletion of P2Y₆R protects mice from diet-induced obesity, improving glucose tolerance and insulin sensitivity with reduced systemic inflammation. These changes were associated with reduced JNK signaling and enhanced expression and activity of PPARα affecting downstream PGC1α levels leading to beiging of white fat. In contrast, P2Y₆R deletion in skeletal muscle reduced glucose uptake, resulting in impaired glucose homeostasi

SUBMITTER: Jain S 

PROVIDER: S-EPMC7720204 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature