Astrocyte-specific deletion of peroxisome-proliferator activated receptor-g impairs glucose metabolism and estrous cycling in female mice

Marina O. Fernandez, Katherine Hsueh, Hyun Tae Park, Consuelo Sauceda, Vicky Hwang, Deepak Kumar, Sun Kim, Emily Rickert, Sumana Mahata, Nicholas J.G. Webster

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Mice lacking peroxisome-proliferator activated receptor-γ (PPARγ) in neurons do not become leptin resistant when placed on a high-fat diet (HFD). In male mice, this results in decreased food intake and increased energy expenditure, causing reduced body weight, but this difference in body weight is not observed in female mice. In addition, estrous cycles are disturbed and the ovaries present with hemorrhagic follicles. We observed that PPARγ was more highly expressed in astrocytes than neurons, so we created an inducible, conditional knockout of PPARγ in astrocytes (AKO). The AKO mice had impaired glucose tolerance and hepatic steatosis that did not worsen with HFD. Expression of gluconeogenic genes was elevated in the mouse livers, as was expression of several genes involved in lipogenesis, lipid transport, and storage. The AKO mice also had a reproductive phenotype with fewer estrous cycles, elevated plasma testosterone levels, reduced corpora lutea formation, and alterations in hypothalamic and ovarian gene expression. Thus, the phenotypes of the AKO mice were very different from those seen in the neuronal knockout mice, suggesting distinct roles for PPARγ in these two cell types.

Original languageEnglish
Pages (from-to)1332-1350
Number of pages19
JournalJournal of the Endocrine Society
Volume1
Issue number11
DOIs
Publication statusPublished - 2017 Nov

Keywords

  • Astrocytes
  • Fertility
  • Glucose intolerance
  • Obesity
  • PPARγamma

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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