PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells

D Cipolletta, M Feuerer, A Li, N Kamei, J Lee… - Nature, 2012 - nature.com
D Cipolletta, M Feuerer, A Li, N Kamei, J Lee, SE Shoelson, C Benoist, D Mathis
Nature, 2012nature.com
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.
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 pro-inflammatory macrophages is considered to be a key event driving …
Abstract
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. 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 pro-inflammatory 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 (Treg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the ‘master regulator’ of adipocyte differentiation, as a crucial molecular orchestrator of VAT Treg cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT Treg 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 Treg cells with unique functions can be precisely targeted to therapeutic ends.
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