Fas and FasL Expression in Human Adipose Tissue Is Related to Obesity, Insulin Resistance, and Type 2 Diabetes
Fas and FasL Expression in Human Adipose Tissue Is Related to Obesity, Insulin Resistance, and Type 2 Diabetes
复制标题
DOI：
10.1210/jc.2013-2488
复制
发表时间：
2014-01-01
影响因子：
5.8
通讯作者：
Konrad, Daniel
中科院分区：
文献类型：
--
作者：
Blueher, Matthias;Kloeting, Nora;Konrad, Daniel
背景：小鼠脂肪细胞死亡受体Fas(CD95)的缺失与胰岛素敏感性的提高和脂肪组织(AT)炎症的减少有关。目的：我们研究AT Fas与人类肥胖的关系。设计和方法：在256名瘦身和肥胖(包括胰岛素敏感和胰岛素抵抗亚组；n=60)受试者的大网膜和皮下AT配对样本中，我们研究了Fas和Fas配体(FasL)mRNA的表达是否具有脂肪库特异性，在肥胖症中发生改变，并与AT炎症和胰岛素敏感性的测量有关。此外，在两步减肥手术策略的背景下，16名肥胖患者在显著减重45+/-6.3 kg后检测了AT Fas mRNA的表达。结果：Fas和FasL在大网膜(OM)中的表达显著高于sc AT。Fas表达与体重指数(OM，r(2)=0.44；sc，r(2)=0.14)、AT巨噬细胞浸润(OM，r(2)=0.36；sc，r(2)=0.16)、正常血糖-高胰岛素钳夹葡萄糖输注率(OM，r(2)=0.17；sc，r(2)=0.13)相关(P<；0.05)。FasL表达与脂肪细胞大小(OM，r(2)=0.32；sc，r(2)=0.17)和AT巨噬细胞浸润(OM，r(2)=0.46；sc，r(2)=0.02)密切相关。胰岛素敏感型肥胖者Fas和FasL的表达显著低于胰岛素抵抗肥胖者。胃袖状切除后12个月体重显著减轻与肥胖症患者外膜和皮下脂肪沉积中Fas表达显著降低有关。结论：肥胖患者胰岛素敏感性降低和血管紧张素转换酶功能紊乱可能与Fas表达增加无关。此外，显著的减肥减少了OM和sc脂肪库中Fas的表达。
Context: Deletion of the death receptor Fas (CD95) in adipocytes of mice is associated with improved insulin sensitivity and reduced adipose tissue (AT) inflammation.Objective: Here we investigate the relationship of AT Fas with human obesity.Design and Methods: In paired samples of omental and sc AT from 256 lean and obese (including insulin-sensitive and insulin-resistant subgroups; n = 60) participants, we investigated whether Fas and Fas-ligand (FasL) mRNA expression is fat depot-specific, altered in obesity, and related to measures of AT inflammation and insulin sensitivity. In addition, AT Fas mRNA expression was measured in 16 obese patients after significant weight loss of 45 +/- 6.3 kg in the context of a two-step bariatric surgery strategy.Results: Fas and FasL are significantly higher expressed in omental (OM) compared to sc AT. Fas expression correlates withbodymass index(OM, r(2) = 0.44; sc, r(2) = 0.14), AT macrophage infiltration (OM, r(2) = 0.36; sc, r(2) = 0.16), and glucose infusion rate in euglycemic-hyperinsulinemic clamps (OM, r(2) = 0.17; sc, r(2) = 0.13) (P < .05 for all). FasL expression most strongly correlates with adipocyte size (OM, r(2) = 0.32; sc, r(2) = 0.17) and AT macrophage infiltration (OM, r(2) = 0.46; sc, r(2) = 0.02). Insulin-sensitive obese individuals had significantly lower Fas and FasL expression than insulin-resistant obese individuals. Significant weight loss 12 months after gastric sleeve resection is associated with a significantly reduced Fas expression in OM and sc fat depots.Conclusions: Independently of body weight, increased Fas expression may contribute to impaired insulin sensitivity and AT dysfunction in obesity. Moreover, significant weight loss reduces Fas expression in OM and sc fat depots.