PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue [T.sub.reg] cells

Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation (1). Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and...

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Bibliographic Details
Published in:Nature (London) 2012-06, Vol.486 (7404), p.549
Main Authors: Cipolletta, Daniela, Feuerer, Markus, Li, Amy, Kamei, Nozomu, Lee, Jongsoon, Shoelson, Steven E, Benoist, Christophe, Mathis, Diane
Format: Article
Language:English
Subjects:
Adipose tissues
Development and progression
Dosage and administration
Drug therapy
Health aspects
Molecular biology
Obesity
Physiological aspects
Thiazolidinediones
Transcription factors
Type 2 diabetes
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Summary:Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation (1). Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by proinflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T ([T.sub.reg]) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity (2). Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT [T.sub.reg] cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT [T.sub.reg] cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of [T.sub.reg] cells with unique functions can be precisely targeted to therapeutic ends.
ISSN:0028-0836
1476-4687
DOI:10.1038/naturelll32