Editors' ChoiceObesity

Obesity and Inflammation: The Fas Connection

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Science Translational Medicine  27 Jan 2010:
Vol. 2, Issue 16, pp. 16ec15
DOI: 10.1126/scitranslmed.3000857

For decades, epidemiologic studies have reported a connection between obesity and inflammation. For example, proinflammatory gene expression and blood levels of inflammation-associated proteins—including tumor necrosis factor–α, interleukin-6, and C-reactive protein—are elevated among obese subjects. The inflammatory milieu is thought to induce a state of local and systemic insulin resistance, contributing to the development of type 2 diabetes. Despite the abundance of epidemiologic evidence, the biological processes linking obesity to the activation of inflammatory pathways are unclear.

The Fas receptor has been well characterized as a regulator of programmed cell death. Now, Wueest et al. propose that Fas may also play an important role in adipose tissue inflammation and obesity-induced metabolic dysregulation. The authors showed that Fas expression is elevated in the adipose tissue of obese and type 2 diabetic patients relative to lean individuals, as well as in mouse models of obesity and insulin resistance. Fas expression was up-regulated in normal mice fed a high-fat diet, which also led to the recruitment of immune cells and the secretion of proinflammatory factors. On the other hand, mice with Fas-deficient adipocytes demonstrated diminished inflammation and were protected from fat accumulation in liver cells and the development of glucose intolerance and systemic insulin resistance, which is normally induced by a high-fat diet. These observations suggest that Fas may activate inflammatory pathways in adipose tissues and contribute to obesity-associated insulin resistance. These data offer an alternative mechanism for the pathogenesis of type 2 diabetes, and suggest that a deeper understanding about the regulation of Fas expression and activation in adipose tissues may lead to new strategies for the prevention and treatment of this prevalent disease

S. Wueest et al., Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice. J. Clin. Invest. 120, 191–202 (2010). [Full Text]

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