上海士鋒生物關于PPAR-γ的重要作用的介紹

在過去的幾十年來，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zui主要是同屬于慢性低級炎癥。持續的營養過剩促使內臟脂肪組織內白細胞的累積和激活，并延伸到其他組織，zui終導致胰島素抵抗、Ⅱ型糖尿病和脂肪肝等代謝異常疾病。

雖然促炎癥巨噬細胞入侵內臟脂肪組織被認為是驅動脂肪組織炎癥和胰島素抵抗的一個關鍵事件，但是我們對其他免疫細胞類型在這些過程中的扮演的角色知道的很少。

zui近，內臟脂肪組織中調節性T細胞的一個*類群被認為參與控制脂肪組織的炎癥狀態，因而，也被認為與胰島素的敏感性相關。

研究表明，過氧化物酶體增生物激活受體γ（PPAR-γ），作為脂肪細胞分化的一個主要的調節子，被確定為協調內臟脂肪組織調節性T細胞的累積、類型和功能的關鍵分子。意外發現，噻唑烷二酮藥物要想*恢復小鼠的胰島素敏感性，內臟脂肪組織調節性T細胞內PPAR-γ的表達是必須的。

這些發現揭示了噻唑烷二酮藥物作用的細胞機制，并證明了具有*功能的調節性T細胞的獨立類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.