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

Nature, 2012/6/28;486(7404):549-53.

Cipolletta D[1], Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, Benoist C, Mathis D

Affiliations

PMID: 22722857DOI: 10.1038/nature11132

Impact factor: 69.504

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.
MeSH terms
Adipose Tissue; Animals; Cell Differentiation; Diabetes Mellitus, Type 2; Epididymis; Forkhead Transcription Factors; Gene Expression; Hypoglycemic Agents; Inflammation; Insulin Resistance; Lymphocyte Count; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; PPAR gamma; Phenotype; Pioglitazone; RNA, Messenger; T-Lymphocytes, Regulatory; Thiazolidinediones; Transcription, Genetic
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