Up-regulation of Bcl-2 during adipogenesis mediates apoptosis resistance in human adipocytes

脂肪生成过程中 Bcl-2 的上调介导人类脂肪细胞凋亡抵抗

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作者:Stella A Nagel, Michaela Keuper, Ivana Zagotta, Eveliina Enlund, Azahara Iris Ruperez, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky

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.

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