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

By D. Cipolletta, M. Feuerer, Amy Li, Nozomu Kamei, Jongsoon Lee, S. Shoelson, C. Benoist, D. Mathis. Nature, 2012

1,109 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/00c1cc10c23bdaf1eb7a8597f805e712c603bdf9

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Citations in the corpus

Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner (2019, background): “Macrophage-specific PPARgamma controls Cell.”
Ablation of PRDM16 and Beige Adipose Causes Metabolic Dysfunction and a Subcutaneous to Visceral Fat Switch (2014, background): “No other immune cell subsets, including T regulatory cells, which have been shown to play a role in metabolic disease (Cipolletta et al., 2012), were altered in adipose tissue or lymphoid organs from KO mice (Figure S5D).”