title: Up-regulation of Bcl-2 during adipogenesis mediates apoptosis resistance in human adipocytes.
abstract: Targeting apoptotic pathways in adipocytes has been suggested as a pharmacological approach to treat obesity. However, adipocyte apoptosis was identified as a cause for macrophage infiltration into adipose tissue. Previous studies suggest that mature adipocytes are less sensitive to apoptotic stimuli as compared to preadipocytes. Here, we aimed to identify proteins mediating apoptosis resistance in adipocytes. Our data revealed that the anti-apoptotic protein Bcl-2 (B-cell lymphoma 2) is up-regulated during adipogenic differentiation. Bcl-2 overexpression in preadipocytes lowers their apoptosis sensitivity to the level of mature adipocytes. Vice versa Bcl-2 knockdown in adipocytes sensitizes these cells to CD95-induced apoptosis. Taken together, our findings suggest a shift in the balance of pro-apoptotic and anti-apoptotic molecules during adipogenesis resulting in a higher apoptosis resistance. This study sheds new light on the apoptotic process in human fat cells and may constitute a new possible target for the specific regulation of adipose tissue mass.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
authors.forename: Stella A
authors.initials: SA
authors.lastname: Nagel
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Keuper
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Zagotta
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
authors.forename: Eveliina
authors.initials: E
authors.lastname: Enlund
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
authors.forename: Azahara Iris
authors.initials: AI
authors.lastname: Ruperez
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany. Electronic address: martin.wabitsch@uniklinik-ulm.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany. Electronic address: pamela.fischer@uniklinik-ulm.de.
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis; D017209:Apoptosis; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor
keywords: Adipocyte; Apoptosis; B-cell lymphoma 2; Bcl-2; CD95; CHX; IGF-1; Obesity; SDHA; SGBS; Simpson-Golabi-Behmel syndrome; cluster of differentiation 95; cycloheximide; insulin-like growth factor-1; succinate dehydrogenase