Fas and FasL expression in human adipose tissue is related to obesity, insulin resistance, and type 2 diabetes.
- Blüher M Department of Medicine (M.B., M.F., M.S.), University of Leipzig, 04103 Leipzig, Germany; Integriertes Forschungs-und Behandlungszentrum Obesity Diseases (N.K.), Junior Research Group Animal Models, University of Leipzig, 04103 Leipzig, Germany; Division of Pediatric Endocrinology and Diabetology and Children's Research Centre (S.W., E.J.S., D.K.), University Children's Hospital, CH-8032 Zurich, Switzerland; Städtisches Klinikum Karlsruhe (M.R.S.), Clinic of Visceral Surgery, 76133 Karlsruhe, Germany; Department of Surgery (A.D.), University of Leipzig, 04103 Leipzig, Germany; and Zurich Center for Integrative Human Physiology (D.K.), University of Zurich, CH-8006 Zurich, Switzerland.
- Klöting N
- Wueest S
- Schoenle EJ
- Schön MR
- Dietrich A
- Fasshauer M
- Stumvoll M
- Konrad D
- 2013-11-02
Published in:
- The Journal of clinical endocrinology and metabolism. - 2014
Adipose Tissue
Adult
Bariatric Surgery
Body Mass Index
Case-Control Studies
Diabetes Mellitus, Type 2
Fas Ligand Protein
Female
Gene Expression
Humans
Insulin Resistance
Male
Middle Aged
Obesity
Thinness
Weight Loss
fas Receptor
English
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, r2=0.44; sc, r2=0.14), AT macrophage infiltration (OM, r2=0.36; sc, r2=0.16), and glucose infusion rate in euglycemic-hyperinsulinemic clamps (OM, r2=0.17; sc, r2=0.13) (P<.05 for all). FasL expression most strongly correlates with adipocyte size (OM, r2=0.32; sc, r2=0.17) and AT macrophage infiltration (OM, r2=0.46; sc, r2=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.
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, r2=0.44; sc, r2=0.14), AT macrophage infiltration (OM, r2=0.36; sc, r2=0.16), and glucose infusion rate in euglycemic-hyperinsulinemic clamps (OM, r2=0.17; sc, r2=0.13) (P<.05 for all). FasL expression most strongly correlates with adipocyte size (OM, r2=0.32; sc, r2=0.17) and AT macrophage infiltration (OM, r2=0.46; sc, r2=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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1210/jc.2013-2488
- PMID 24178789
- Persistent URL
- https://sonar.ch/global/documents/165946
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