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Role of CD95-Mediated Adipocyte Loss in Autoimmune Lipodystrophy

Department of Pediatrics and Adolescent Medicine (P.F.-P., G.S., K.-M.D., M.W.), University of Ulm, D-89075 Ulm, Germany; University Children’s Hospital (H.H.), University of Würzburg, D-97080 Würzburg, Germany; Clinic for Plastic Surgery (A.K.H.), D-89073 Ulm, Germany; and Department of Pathology (P.M.), University of Ulm, D-89081 Ulm, Germany

Address all correspondence and requests for reprints to: Prof. Dr. Martin Wabitsch, Pediatric Endocrinology, Department of Pediatrics and Adolescent Medicine, University of Ulm, Prittwitzstrasse 43, 89075 Ulm, Germany. E-mail: martin.wabitsch{at}medizin.uni-ulm.de.

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- and TNF-. In vitro studies with human adipocytes demonstrated that interferon- and TNF- 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.

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