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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Uridine diphosphate (UDP)-activated purinergic receptor P2Y 6 (P2Y 6 R) plays a crucial role in controlling energy balance through central mechanisms. However, P2Y 6 R's roles in peripheral tissues regulating energy and glucose homeostasis remain unexplored. Here, we report the surprising finding that adipocyte-specific deletion of P2Y 6 R 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, P2Y 6 R deletion in skeletal muscle reduced glucose uptake, resulting in impaired glucose homeostasis. Interestingly, whole body P2Y 6 R knockout mice showed metabolic improvements similar to those observed with mice lacking P2Y 6 R only in adipocytes. Our findings provide compelling evidence that P2Y 6 R antagonists may prove useful for the treatment of obesity and type 2 diabetes.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.