title: Role of CD95-mediated adipocyte loss in autoimmune lipodystrophy.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  We have identified here a possible mechanism responsible for the loss of adipocytes by apoptosis in autoimmune lipodystrophy.
authors.affiliation: Pediatric Endocrinology, Department of Pediatrics and Adolescent Medicine, University of Ulm, Prittwitzstrasse 43, 89075 Ulm, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.forename: Helge
authors.initials: H
authors.lastname: Hebestreit
authors.forename: Albert K
authors.initials: AK
authors.lastname: Hofmann
authors.forename: Gudrun
authors.initials: G
authors.lastname: Strauss
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
mesh_terms: D017667:Adipocytes / Q000276:immunology* / Q000473:pathology; D015703:Antigens, CD / Q000502:physiology; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D018929:Cell Culture Techniques; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008060:Lipodystrophy / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D019014:fas Receptor