在過(guò)去的幾十年來(lái)，肥胖和Ⅱ型糖尿病同步急劇增加。這兩種代謝紊亂癥的一個(gè)zui主要是同屬于慢性低級(jí)炎癥。持續(xù)的營(yíng)養(yǎng)過(guò)剩促使內(nèi)臟脂肪組織內(nèi)白細(xì)胞的累積和激活，并延伸到其他組織，zui終導(dǎo)致胰島素抵抗、Ⅱ型糖尿病和脂肪肝等代謝異常疾病。
雖然促炎癥巨噬細(xì)胞入侵內(nèi)臟脂肪組織被認(rèn)為是驅(qū)動(dòng)脂肪組織炎癥和胰島素抵抗的一個(gè)關(guān)鍵事件，但是我們對(duì)其他免疫細(xì)胞類(lèi)型在這些過(guò)程中的扮演的角色知道的很少。
zui近，內(nèi)臟脂肪組織中調(diào)節(jié)性T細(xì)胞的一個(gè)*類(lèi)群被認(rèn)為參與控制脂肪組織的炎癥狀態(tài)，因而，也被認(rèn)為與胰島素的敏感性相關(guān)。
研究表明，過(guò)氧化物酶體增生物激活受體γ（PPAR-γ），作為脂肪細(xì)胞分化的一個(gè)主要的調(diào)節(jié)子，被確定為協(xié)調(diào)內(nèi)臟脂肪組織調(diào)節(jié)性T細(xì)胞的累積、類(lèi)型和功能的關(guān)鍵分子。意外發(fā)現(xiàn)，噻唑烷二酮藥物要想*恢復(fù)小鼠的胰島素敏感性，內(nèi)臟脂肪組織調(diào)節(jié)性T細(xì)胞內(nèi)PPAR-γ的表達(dá)是必須的。
這些發(fā)現(xiàn)揭示了噻唑烷二酮藥物作用的細(xì)胞機(jī)制，并證明了具有*功能的調(diào)節(jié)性T細(xì)胞的獨(dú)立類(lèi)群能地用于治療疾病。
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells
Daniela Cipolletta，Markus Feuerer，Amy Li，Nozomu Kamei，Jongsoon Lee，Steven E. Shoelson，Christophe Benoist&Diane Mathis
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 inflammation1. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue （VAT） and ultimay 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 sensitivity2. 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.
