The Role of the Prostaglandin E2 EP3 Receptor in Obesity, Insulin Resistance, and Glycemic Control
dc.creator | Ceddia, Ryan Patrick | |
dc.date.accessioned | 2020-08-23T15:53:18Z | |
dc.date.available | 2017-12-01 | |
dc.date.issued | 2015-12-01 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-11242015-165031 | |
dc.identifier.uri | http://hdl.handle.net/1803/14790 | |
dc.description.abstract | Mice carrying a targeted disruption of the prostaglandin E2 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. While 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, MCP-1, IL-6 expression, and necrosis in their epididymal fat pads as compared to 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 of isoproterenol stimulated lipolysis compared to EP3+/+. EP3-/- 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-/- mice became hyperglycemic and hyperinsulinemic when compared to EP3+/+ fed HFD, demonstrating a more severe insulin resistance phenotype in EP3-/-. These results demonstrate that when fed a HFD, EP3-/- mice have abnormal lipid distribution, developing excessive ectopic lipid accumulation and associated insulin resistance. | |
dc.format.mimetype | application/pdf | |
dc.subject | GPCR | |
dc.subject | knock-out | |
dc.subject | lipid distribution | |
dc.subject | lipolysis | |
dc.subject | metabolism | |
dc.subject | adipose | |
dc.subject | adipocyte | |
dc.subject | pancreas | |
dc.subject | NSAID | |
dc.subject | inflammation | |
dc.subject | triglyceride | |
dc.subject | free fatty acid | |
dc.subject | glucose | |
dc.subject | lipid | |
dc.subject | islet | |
dc.subject | mouse | |
dc.subject | diabetes | |
dc.subject | EP3 | |
dc.subject | PGE2 | |
dc.subject | prostaglandin | |
dc.subject | obesity | |
dc.subject | insulin | |
dc.title | The Role of the Prostaglandin E2 EP3 Receptor in Obesity, Insulin Resistance, and Glycemic Control | |
dc.type | dissertation | |
dc.contributor.committeeMember | Richard M. Breyer | |
dc.contributor.committeeMember | Maureen A. Gannon | |
dc.contributor.committeeMember | James M. Luther | |
dc.contributor.committeeMember | Owen P. McGuinness | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Pharmacology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2017-12-01 | |
local.embargo.lift | 2017-12-01 | |
dc.contributor.committeeChair | Kevin P. Currie |
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Electronic theses and dissertations of masters and doctoral students submitted to the Graduate School.