Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice
| Autor: | Marc Y. Donath, Alexander V. Chervonsky, Desiree M. Schumann, Daniel Konrad, Julia M. Rytka, Anita Schildknecht, Eugen J. Schoenle, Reto A. Rapold, Ori Nov, Assaf Rudich, Stephan Wueest |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
FGF21 medicine.medical_treatment Adipose tissue macrophages Adipose tissue White adipose tissue Biology Fatty Acid-Binding Proteins Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance 3T3-L1 Cells Internal medicine Adipocytes medicine Animals Humans Obesity fas Receptor 030304 developmental biology Inflammation Mice Knockout 0303 health sciences Insulin General Medicine medicine.disease Fas receptor Dietary Fats Fatty Liver Mice Inbred C57BL Endocrinology Adipose Tissue 030220 oncology & carcinogenesis Female Insulin Resistance |
| Zdroj: | Journal of Clinical Investigation. 120:191-202 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci38388 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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