The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice

Mice carrying a targeted disruption of the prostaglandin E2 (PGE2) E-prostanoid receptor 3 (EP3) gene, Ptger3, were fed a high-fat diet (HFD), or a micronutrient matched control diet, to investigate the effects of disrupted PGE2-EP3 signaling on diabetes in a setting of diet-induced obesity. Although no differences in body weight were seen in mice fed the control diet, when fed a HFD, EP3−/− mice gained more weight relative to EP3+/+ mice. Overall, EP3−/− mice had increased epididymal fat mass and adipocyte size; paradoxically, a relative decrease in both epididymal fat pad mass and adipocyte size was observed in the heaviest EP3−/− mice. The EP3−/− mice had increased macrophage infiltration, TNF-α, monocyte chemoattractant protein-1, IL-6 expression, and necrosis in their epididymal fat pads as compared with EP3+/+ animals. Adipocytes isolated from EP3+/+ or EP3−/− mice were assayed for the effect of PGE2-evoked inhibition of lipolysis. Adipocytes isolated from EP3−/− mice lacked PGE2-evoked inhibition o...