Abstract
Sterile inflammation of visceral fat, provoked by dying adipocytes, links the metabolic syndrome to cardiovascular disease. Danger-associated molecular patterns, such as adenosine triphosphate (ATP), are released by activated or dying cells and orchestrate leukocyte infiltration and inflammation via the purinergic receptor P2Y
. The gene expression of ATP receptor P2Y
did not change in several tissues in the course of obesity, but was increased within epididymal fat. Adipose tissue from P2Y
mice consuming high-fat diet (HFD) contained less crown-like structures with a reduced frequency of adipose tissue macrophages (ATMs). This was likely due to decreased leukocyte migration because of missing VCAM-1 exposition on P2Y
deficient hypertrophic adipose tissue endothelial cells. Accordingly, P2Y
mice showed blunted traits of the metabolic syndrome: they gained less weight compared to P2Y
controls, while intake of food and movement behaviour remained unchanged. Liver and adipose tissue were smaller in P2Y
animals. Insulin tolerance testing (ITT) performed in obese P2Y
mice revealed a better insulin sensitivity as well as lower plasma C-peptide and cholesterol levels. We demonstrate that interfering with somatic P2Y
signalling prevents excessive immune cell deposition in diet-induced obesity (DIO), both attenuating adipose tissue inflammation and ameliorating the metabolic phenotype. Thus, blocking the P2Y
cascade may be a promising strategy to limit metabolic disease and its sequelae.