Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89075 Ulm, Germany.
Mol Cell Endocrinol. 2014 Jan 25;382(1):368-376. doi: 10.1016/j.mce.2013.10.024. Epub 2013 Oct 26.
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.
靶向脂肪细胞中的凋亡途径已被提议作为治疗肥胖症的药理学方法。然而，脂肪细胞凋亡已被确定为巨噬细胞浸润脂肪组织的原因。先前的研究表明，与前体脂肪细胞相比，成熟脂肪细胞对凋亡刺激的敏感性较低。在这里，我们旨在确定介导脂肪细胞抗凋亡的蛋白质。我们的数据表明，凋亡抑制蛋白 Bcl-2（B 细胞淋巴瘤 2）在脂肪生成分化过程中上调。在前体脂肪细胞中过表达 Bcl-2 会降低其对凋亡刺激的敏感性，使其与成熟脂肪细胞的水平相当。相反，在脂肪细胞中敲低 Bcl-2 会使这些细胞对 CD95 诱导的凋亡敏感。总之，我们的研究结果表明，在脂肪生成过程中，促凋亡和抗凋亡分子之间的平衡发生了变化，导致凋亡抵抗性增加。这项研究为人类脂肪细胞的凋亡过程提供了新的认识，并可能成为特定调节脂肪组织质量的新的可能靶标。
