PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells.
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells.
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DOI：
10.1038/nature11132
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发表时间：
2012-06-28
期刊：
影响因子：
64.8
通讯作者：
Mathis, Diane
中科院分区：
文献类型：
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作者：
Cipolletta, Daniela;Feuerer, Markus;Li, Amy;Kamei, Nozomu;Lee, Jongsoon;Shoelson, Steven E.;Benoist, Christophe;Mathis, Diane
肥胖和2型糖尿病（T2D）在过去几十年中同时急剧增加。这两种疾病之间的主要联系之一是慢性低度炎症。长期营养过剩会促进白细胞在内脏脂肪组织（VAT）中的积累和活化，最终导致其他组织，从而引起代谢异常，如胰岛素抵抗、T2D和脂肪肝。虽然促炎巨噬细胞对VAT的入侵被认为是驱动脂肪组织炎症和胰岛素抵抗的关键事件，但对其他免疫系统细胞类型在这些过程中的作用知之甚少。最近，一个独特的人口的增值税驻地调节性T细胞（THEORY）涉及控制的炎症状态的脂肪组织，从而，胰岛素敏感性。我们已经确定了过氧化物酶体增殖物激活受体γ（PPARγ），脂肪细胞分化的“主调节因子”，作为VAT Treg积累、表型和功能的关键分子协调者。出乎意料的是，在噻唑烷二酮（TZD）药物吡格列酮（Pio）完全恢复肥胖小鼠的胰岛素敏感性时，VAT Tactinase的PPARγ表达是必需的。这些发现表明了这类重要的T2D药物的一种以前未知的细胞机制，并提供了具有独特功能的T2D离散群体可以精确靶向治疗目的的原理证明。
Obesity and type-2 diabetes (T2D) have increased dramatically over the past several 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, which provokes metabolic abnormalities such as insulin resistance, T2D and fatty-liver disease. While 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. Recently, a unique population of VAT-resident regulatory T cells (Tregs) was implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity . We have identified peroxisome proliferator-activated receptor gamma (PPARγ), the “master-regulator” of adipocyte differentiation, as a critical molecular orchestrator of VAT Treg accumulation, phenotype and function. Unexpectedly, PPARγ expression by VAT Tregs was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione (TZD) drug, pioglitazone (Pio). These findings suggest a previously unknown cellular mechanism for this important class of T2D drugs, and provide proof-of-principle that discrete populations of Tregs with unique functions can be precisely targeted to therapeutic ends.
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