Brain PPAR-γ promotes obesity and is required for the insulin–sensitizing effect of thiazolidinediones View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-05

AUTHORS

Min Lu, David A Sarruf, Saswata Talukdar, Shweta Sharma, Pingping Li, Gautam Bandyopadhyay, Sarah Nalbandian, WuQiang Fan, Jiaur R Gayen, Sushil K Mahata, Nicholas J Webster, Michael W Schwartz, Jerrold M Olefsky

ABSTRACT

In adipose tissue, muscle, liver and macrophages, signaling by the nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) is a determinant of insulin sensitivity and this receptor mediates the insulin-sensitizing effects of thiazolidinediones (TZDs). As PPAR-γ is also expressed in neurons, we generated mice with neuron-specific Pparg knockout (Pparg brain knockout (BKO)) to determine whether neuronal PPAR-γ signaling contributes to either weight gain or insulin sensitivity. During high-fat diet (HFD) feeding, food intake was reduced and energy expenditure increased in Pparg-BKO mice compared to Pparg(f/f) mice, resulting in reduced weight gain. Pparg-BKO mice also responded better to leptin administration than Pparg(f/f) mice. When treated with the TZD rosiglitazone, Pparg-BKO mice were resistant to rosiglitazone-induced hyperphagia and weight gain and, relative to rosiglitazone-treated Pparg(f/f) mice, experienced only a marginal improvement in glucose metabolism. Hyperinsulinemic euglycemic clamp studies showed that the increase in hepatic insulin sensitivity induced by rosiglitazone treatment during HFD feeding was completely abolished in Pparg-BKO mice, an effect associated with the failure of rosiglitazone to improve liver insulin receptor signal transduction. We conclude that excess weight gain induced by HFD feeding depends in part on the effect of neuronal PPAR-γ signaling to limit thermogenesis and increase food intake. Neuronal PPAR-γ signaling is also required for the hepatic insulin sensitizing effects of TZDs. More... »

PAGES

618

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2332

DOI

http://dx.doi.org/10.1038/nm.2332

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1037960745

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21532596


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nm.2332'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nm.2332'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nm.2332'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nm.2332'


 

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