Fas and FasL Expression in Human Adipose Tissue Is Related to Obesity, Insulin Resistance, and Type 2 Diabetes

被引:45
作者
Blueher, Matthias [1 ]
Kloeting, Nora [2 ]
Wueest, Stephan [3 ,4 ]
Schoenle, Eugen J. [3 ,4 ]
Schoen, Michael R. [5 ]
Dietrich, Arne [6 ]
Fasshauer, Mathias [1 ]
Stumvoll, Michael [1 ]
Konrad, Daniel [3 ,4 ,7 ]
机构
[1] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany
[2] Univ Leipzig, Jr Res Grp Anim Models, Integriertes Forsch & Behandlungszentrum Obes Dis, D-04103 Leipzig, Germany
[3] Univ Childrens Hosp, Div Pediat Endocrinol & Diabetol, CH-8032 Zurich, Switzerland
[4] Univ Childrens Hosp, Childrens Res Ctr, CH-8032 Zurich, Switzerland
[5] Clin Visceral Surg, Stadt Klinikum Karlsruhe, D-76133 Karlsruhe, Germany
[6] Univ Leipzig, Dept Surg, D-04103 Leipzig, Germany
[7] Univ Zurich, Ctr Integrat Human Physiol, CH-8006 Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
MACROPHAGE INFILTRATION; ADIPOCYTE APOPTOSIS; GENE-EXPRESSION; INFLAMMATION; STRESS; ORIGIN; LINK;
D O I
10.1210/jc.2013-2488
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:E36 / E44
页数:9
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