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Overexpression of PPARγ specifically in pancreatic β-cells exacerbates obesity-induced glucose intolerance, reduces β-cell mass, and alters islet lipid metabolism in male mice.
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2014 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 155, no 10, 3843-52 p.Article in journal (Refereed) Published
Abstract [en]

The contribution of peroxisomal proliferator-activated receptor (PPAR)-γ agonism in pancreatic β-cells to the antidiabetic actions of thiazolidinediones has not been clearly elucidated. Genetic models of pancreatic β-cell PPARγ ablation have revealed a potential role for PPARγ in β-cell expansion in obesity but a limited role in normal β-cell physiology. Here we overexpressed PPARγ1 or PPARγ2 specifically in pancreatic β-cells of mice subjected to high-fat feeding using an associated adenovirus (β-PPARγ1-HFD and β-PPARγ2-HFD mice). We show β-cell-specific PPARγ1 or PPARγ2 overexpression in diet-induced obese mice exacerbated obesity-induced glucose intolerance with decreased β-cell mass, increased islet cell apoptosis, and decreased plasma insulin compared with obese control mice (β-eGFP-HFD mice). Analysis of islet lipid composition in β-PPARγ2-HFD mice revealed no significant changes in islet triglyceride content and an increase in only one of eight ceramide species measured. Interestingly β-PPARγ2-HFD islets had significantly lower levels of lysophosphatidylcholines, lipid species shown to enhance insulin secretion in β-cells. Gene expression profiling revealed increased expression of uncoupling protein 2 and genes involved in fatty acid transport and β-oxidation. In summary, transgenic overexpression of PPARγ in β-cells in diet-induced obesity negatively impacts whole-animal carbohydrate metabolism associated with altered islet lipid content, increased expression of β-oxidative genes, and reduced β-cell mass.

Place, publisher, year, edition, pages
2014. Vol. 155, no 10, 3843-52 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:oru:diva-63696DOI: 10.1210/en.2014-1076PubMedID: 25051434OAI: oai:DiVA.org:oru-63696DiVA: diva2:1169261
Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2017-12-22

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CiteExportLink to record
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