Cipolletta, DanielaFeuerer, MarkusLi, AmyKamei, NozomuLee, JongsoonShoelson, StevenBenoist, ChristopheMathis, Diane2013-05-032012Cipolletta, Daniela, Markus Feuerer, Amy Li, Nozomu Kamei, Jongsoon Lee, Steven E. Shoelson, Christophe O. Benoist, and Diane J. Mathis. 2012. PPARγ is a major driver of the accumulation and phenotype of adipose-tissue \(T_{reg}\) cells. Nature 486(7404): 549-553.0028-08361476-4687http://nrs.harvard.edu/urn-3:HUL.InstRepos:10610379Obesity 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 \((T_{reg})\) 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 \(T_{reg}\) cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT \(T_{reg}\) 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 \(T_{reg}\) cells with unique functions can be precisely targeted to therapeutic ends.en-USregulatory T celladipose tissueobesitytype-2 diabetesnuclear receptorTZD drugJournal Article2013-05-0310.1038/nature11132