A role for central nervous system PPAR-γ in the regulation of energy balance View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-05

AUTHORS

Karen K Ryan, Bailing Li, Bernadette E Grayson, Emily K Matter, Stephen C Woods, Randy J Seeley

ABSTRACT

The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences. PPAR-γ is the target of the thiazolidinedione (TZD) class of insulin-sensitizing drugs, which have been widely prescribed to treat type 2 diabetes mellitus. A common side effect of treatment with TZDs is weight gain. Here we report a previously unknown role for central nervous system (CNS) PPAR-γ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPAR-γ, by either TZDs or hypothalamic overexpression of a fusion protein consisting of PPAR-γ and the viral transcriptional activator VP16 (VP16-PPAR-γ), led to positive energy balance in rats. Blocking the endogenous activation of CNS PPAR-γ with pharmacological antagonists or reducing its expression with shRNA led to negative energy balance, restored leptin sensitivity in high-fat-diet (HFD)-fed rats and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity. More... »

PAGES

623

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2349

DOI

http://dx.doi.org/10.1038/nm.2349

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051675151

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21532595


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