Role of CD95-mediated adipocyte loss in autoimmune lipodystrophy.


CONTEXT Lipodystrophies are rare disorders characterized by the selective loss of adipose tissue. Metabolic complications increase in severity with the extent of fat loss. In some forms of acquired lipodystrophy, the loss of fat is suggested to be a result of autoimmune destruction of adipocytes. Here, the pathogenic mechanism is still poorly understood. OBJECTIVE We have analyzed sc adipose tissue from a 5-yr-old girl with ongoing fat loss by immunohistochemistry. Using cultured human preadipocytes and adipocytes, we elucidated a possible mechanism leading to adipocyte loss in this patient. RESULTS Analysis of adipose tissue samples of the patient with acquired lipodystrophy obtained from skin areas affected by panniculitis suggested that loss of adipocytes was mediated by CD95-induced apoptosis. Regression of adipose tissue was accompanied by lymphohistiocytic infiltration/inflammation and increased serum levels of inflammatory cytokines interferon-gamma and TNF-alpha. In vitro studies with human adipocytes demonstrated that interferon-gamma and TNF-alpha are able to up-regulate CD95 expression and enhance CD95-death-inducing signaling complex formation resulting in a robust sensitization for CD95-mediated apoptosis. CONCLUSION We have identified here a possible mechanism responsible for the loss of adipocytes by apoptosis in autoimmune lipodystrophy.

Cite this paper

@article{FischerPosovszky2006RoleOC, title={Role of CD95-mediated adipocyte loss in autoimmune lipodystrophy.}, author={Pamela Fischer-Posovszky and Helge Uwe Hebestreit and Albert Hofmann and Gudrun Strauss and Peter L Moeller and Klaus Michael Debatin and Martin Wabitsch}, journal={The Journal of clinical endocrinology and metabolism}, year={2006}, volume={91 3}, pages={1129-35} }