Hebbard, Lionel, and George, Jacob (2010) The chicken or the egg: adipocytes and hepatic insulin resistance. Hepatology, 51 (3). pp. 1076-1079.

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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.

Item ID:	40169
Item Type:	Article (Commentary)
ISSN:	1527-3350
Additional Information:	Comment to Wueest S, Rapold RA, Schumann DM, Rytka JM, Schildknecht A, Nov O, et al. Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice. J Clin Invest 2010;120:191-202.
Date Deposited:	31 Aug 2015 00:25
FoR Codes:	06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060104 Cell Metabolism @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 100%
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