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Overall, EP3\u2212\/\u2212 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\u2212\/\u2212 mice. The EP3\u2212\/\u2212 mice had increased macrophage infiltration, TNF-\u03b1, 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\u2212\/\u2212 mice were assayed for the effect of PGE2-evoked inhibition of lipolysis. Adipocytes isolated from EP3\u2212\/\u2212 mice lacked PGE2-evoked inhibition of isoproterenol stimulated lipolysis compared with EP3+\/+. EP3\u2212\/\u2212 mice fed HFD had exaggerated ectopic lipid accumulation in skeletal muscle and liver, with evidence of hepatic steatosis. Both blood glucose and plasma insulin levels were similar between genotypes on a control diet, but when fed HFD, EP3\u2212\/\u2212 mice became hyperglycemic and hyperinsulinemic when compared with EP3+\/+ fed HFD, demonstrating a more severe insulin resistance phenotype in EP3\u2212\/\u2212. These results demonstrate that when fed a HFD, EP3\u2212\/\u2212 mice have abnormal lipid distribution, developing excessive ectopic lipid accumulation and associated insulin resistance.<\/jats:p>","DOI":"10.1210\/en.2015-1693","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T13:47:45Z","timestamp":1445348865000},"page":"220-232","source":"Crossref","is-referenced-by-count":77,"title":["The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice"],"prefix":"10.1210","volume":"157","author":[{"given":"Ryan P.","family":"Ceddia","sequence":"first","affiliation":[{"name":"Departments of Pharmacology (R.P.C., G.M., R.M.B.) 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