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PMID: 19955656 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice.

The Journal of clinical investigation ·Vol. 120 ·No. 1 ·2010-01-00 ·Pages 191-202

Wueest S, Rapold RA, Schumann DM, Rytka JM, Schildknecht A, Nov O, Chervonsky AV, Rudich A, Schoenle EJ, Donath MY, Konrad D

Abstract

Adipose tissue inflammation is linked to the pathogenesis of insulin resistance. In addition to exerting death-promoting effects, the death receptor Fas (also known as CD95) can activate inflammatory pathways in several cell lines and tissues, although little is known about the metabolic consequence of Fas activation in adipose tissue. We therefore sought to investigate the contribution of Fas in adipocytes to obesity-associated metabolic dysregulation. Fas expression was markedly increased in the adipocytes of common genetic and diet-induced mouse models of obesity and insulin resistance, as well as in the adipose tissue of obese and type 2 diabetic patients. Mice with Fas deficiency either in all cells or specifically in adipocytes (the latter are referred to herein as AFasKO mice) were protected from deterioration of glucose homeostasis induced by high-fat diet (HFD). Adipocytes in AFasKO mice were more insulin sensitive than those in wild-type mice, and mRNA levels of proinflammatory factors were reduced in white adipose tissue. Moreover, AFasKO mice were protected against hepatic steatosis and were more insulin sensitive, both at the whole-body level and in the liver. Thus, Fas in adipocytes contributes to adipose tissue inflammation, hepatic steatosis, and insulin resistance induced by obesity and may constitute a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes.

MeSH Terms
3T3-L1 Cells Adipocytes/metabolism Adipose Tissue/pathology Animals Dietary Fats/administration & dosage Fatty Acid-Binding Proteins/physiology Fatty Liver/etiology Female Humans Inflammation/etiology Insulin Resistance Mice Mice, Inbred C57BL Mice, Knockout Obesity/complications,metabolism fas Receptor/physiology
Chemicals
Dietary Fats Fabp4 protein, mouse Fatty Acid-Binding Proteins fas Receptor
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Wueest Stephan
Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Steinwiesstrasse 75, Zurich, Switzerland.
Rapold Reto A
Schumann Desiree M
Rytka Julia M
Schildknecht Anita
Nov Ori
Chervonsky Alexander V
Rudich Assaf
Schoenle Eugen J
Donath Marc Y
Konrad Daniel
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
1558-8238
DOI
10.1172/JCI38388
Published
2010-01-00
Epub
2009-00-01
Pages
191-202
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC2798678
Subset
IM
Corrections
CommentIn
PMID: 20198702
External Links
PubMed source DOI: 10.1172/JCI38388 PMC Full Text View journal details
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