Adipocyte purinergic receptors activated by uracil nucleotides as obesity and type 2 diabetes targets.

Extracellular uridine nucleotides regulate physiological and pathophysiological metabolic processes through the activation of P2Y2, P2Y4, P2Y6 and P2Y14 purinergic receptors, which play a key role in adipogenesis, glucose uptake, lipolysis and adipokine secretion. Using adipocyte-specific knockout mouse models, it has been demonstrated that lack of the P2Y6R or P2Y14R can protect against diet-induced obesity and improve whole-body glucose metabolism. The P2Y2R facilitated adipogenesis and inflammation, and the loss of P2Y4R or P2Y14R raised the levels of the protective endocrine factor adiponectin. Hence, potent antagonists for these receptors may be tested to identify drug candidates for the treatment of obesity and type 2 diabetes. However, future studies are required to provide insight into purinergic regulation of brown adipocytes and their role in thermogenesis. This review summarizes the current studies on uridine nucleotide-activated P2YRs and their role in adipocyte function, diet-induced obesity and associated metabolic deficits.