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TRAIL (TNF-related apoptosis-inducing ligand) inhibits human adipocyte differentiation via caspase-mediated downregulation of adipogenic transcription factors.
Zoller, Verena; Funcke, Jan-Bernd; Keuper, Michaela; Abd El Hay, Muad; Debatin, Klaus-Michael; Wabitsch, Martin; Fischer-Posovszky, Pamela.
Afiliación
  • Zoller V; Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Funcke JB; Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Keuper M; Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Abd El Hay M; Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Debatin KM; Department of Pediatric and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Wabitsch M; Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Fischer-Posovszky P; Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
Cell Death Dis ; 7(10): e2412, 2016 10 13.
Article en En | MEDLINE | ID: mdl-27735943
Tumor necrosis factor-α (TNFα) and other ligands of the TNF superfamily are potent regulators of adipose tissue metabolism and play a crucial role in the obesity-induced inflammation of adipose tissue. Adipose tissue expression levels of TRAIL (TNF-related apoptosis-inducing ligand) and its receptor were shown to be upregulated by overfeeding and decreased by fasting in mice. In the present study we aimed to elucidate the impact of TRAIL on adipogenesis. To this end, human Simpson-Golabi-Behmel syndrome (SGBS) preadipocytes as well as stromal-vascular cells isolated from human white adipose tissue were used as model systems. Human recombinant TRAIL inhibited adipogenic differentiation in a dose-dependent manner. It activated the cleavage of caspase-8 and -3, which in turn resulted in a downregulation of the key adipogenic transcription factors C/EBPα, C/EBPδ, and PPARγ. The effect was completely blocked by pharmacological or genetic inhibition of caspases. Taken together we discovered a so far unrecognized function of TRAIL in the regulation of adipogenesis. Targeting the TRAIL/TRAIL receptor system might provide a novel strategy to interfere with adipose tissue homeostasis.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Regulación hacia Abajo / Diferenciación Celular / Adipocitos / Caspasas / Adipogénesis / Ligando Inductor de Apoptosis Relacionado con TNF Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Regulación hacia Abajo / Diferenciación Celular / Adipocitos / Caspasas / Adipogénesis / Ligando Inductor de Apoptosis Relacionado con TNF Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido