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Fas and FasL expression in human adipose tissue is related to obesity, insulin resistance, and type 2 diabetes.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2014 Jan; Vol. 99 (1), pp. E36-44. Date of Electronic Publication: 2013 Dec 20. - Publication Year :
- 2014
-
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.<br />Objective: Here we investigate the relationship of AT Fas with human obesity.<br />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.<br />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.<br />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.
- Subjects :
- Adult
Bariatric Surgery
Body Mass Index
Case-Control Studies
Diabetes Mellitus, Type 2 metabolism
Fas Ligand Protein metabolism
Female
Gene Expression
Humans
Male
Middle Aged
Obesity metabolism
Obesity surgery
Thinness genetics
Thinness metabolism
Weight Loss genetics
fas Receptor metabolism
Adipose Tissue metabolism
Diabetes Mellitus, Type 2 genetics
Fas Ligand Protein genetics
Insulin Resistance genetics
Obesity genetics
fas Receptor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 99
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 24178789
- Full Text :
- https://doi.org/10.1210/jc.2013-2488