Lack of adipocyte purinergic P2Y <sub>6</sub> receptor greatly improves whole body glucose homeostasis
Shanu Jain, Sai P. Pydi, Kiran S. Toti, Bernard Robaye, Marco Idzko, Oksana Gavrilova, Jürgen Wess, Kenneth A. Jacobson
Abstract
Significance The prevalence of obesity and type 2 diabetes (T2D) has increased worldwide. Obesity is correlated with unfavorable adipose tissue modifications that lead to metabolic dysregulation. Here, we show that P2Y 6 R deficiency in adipocytes protects from diet-induced obesity due to enhanced energy expenditure, reduced inflammation, and white adipose tissue browning. Further, adipocytes lacking P2Y 6 R show reduced JNK expression and activity, contributing to the improved phenotype. This proof-of-concept study strongly suggests that P2Y 6 R antagonists may be beneficial for the treatment of obesity and T2D.
Topics & Concepts
Purinergic receptorAdipose tissueEndocrinologyInternal medicineAdipocyteObesityWhite adipose tissueInflammationType 2 diabetesGlucose homeostasisBrown adipose tissueReceptorBiologyDiabetes mellitusMedicineInsulin resistanceAdenosine and Purinergic SignalingAdipose Tissue and MetabolismCardiovascular, Neuropeptides, and Oxidative Stress Research