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Fas and FasL expression in human adipose tissue is related to obesity, insulin resistance, and type 2 diabetes


Blüher, Matthias; Klöting, Nora; Wueest, Stephan; Schoenle, Eugen J; Schön, Michael R; Dietrich, Arne; Fasshauer, Mathias; Stumvoll, Michael; Konrad, Daniel (2014). Fas and FasL expression in human adipose tissue is related to obesity, insulin resistance, and type 2 diabetes. Journal of Clinical Endocrinology & Metabolism, 99(1):E36-E44.

Abstract

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 with body mass 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.

Abstract

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 with body mass 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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2014
Deposited On:11 Mar 2014 13:25
Last Modified:07 Dec 2017 08:29
Publisher:Endocrine Society
ISSN:0021-972X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1210/jc.2013-2488
PubMed ID:24178789

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