Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Su Sahlgrenska, Vita Stråket 11, 413 45, Gothenburg, Sweden.
Department of Anatomy and Cell Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.
Sci Rep. 2021 Jul 8;11(1):14177. doi: 10.1038/s41598-021-93450-y.
Obesity has previously been thought to protect bone since high body weight and body mass index are associated with high bone mass. However, some more recent studies suggest that increased adiposity negatively impacts bone mass. Here, we aimed to test whether acute loss of adipose tissue, via adipocyte apoptosis, alters bone mass in age-related obese mice. Adipocyte apoptosis was induced in obese male FAT-ATTAC mice through AP20187 dimerizer-mediated activation of caspase 8 selectively in adipocytes. In a short-term experiment, dimerizer was administered to 5.5 month-old mice that were terminated 2 weeks later. At termination, the total fat mass weighed 58% less in dimerizer-treated mice compared with vehicle-treated controls, but bone mass did not differ. To allow for the detection of long-term effects, we used 9-month-old mice that were terminated six weeks after dimerizer administration. In this experiment, the total fat mass weighed less (- 68%) in the dimerizer-treated mice than in the controls, yet neither bone mass nor biomechanical properties differed between groups. Our findings show that adipose tissue loss, despite the reduced mechanical loading, does not affect bone in age-related obese mice. Future studies are needed to test whether adipose tissue loss is beneficial during more severe obesity.
肥胖先前被认为能保护骨骼,因为高体重和体重指数与高骨量有关。然而,一些更新的研究表明,脂肪过多会对骨量产生负面影响。在这里,我们旨在测试通过脂肪细胞凋亡急性丧失脂肪组织是否会改变肥胖相关老年小鼠的骨量。通过 AP20187 二聚体介导的 caspase 8 在脂肪细胞中的选择性激活,在肥胖雄性 FAT-ATTAC 小鼠中诱导脂肪细胞凋亡。在短期实验中,将二聚体施用于 5.5 个月大的小鼠,2 周后处死。在处死时,与载体处理的对照组相比,二聚体处理的小鼠的总脂肪质量减轻了 58%,但骨量没有差异。为了检测长期效应,我们使用了 9 个月大的小鼠,在二聚体给药后 6 周处死。在这个实验中,与对照组相比,二聚体处理的小鼠的总脂肪质量减轻了 68%,但骨量和生物力学特性在两组之间没有差异。我们的研究结果表明,尽管机械负荷减少,但脂肪组织的丧失不会影响肥胖相关老年小鼠的骨骼。需要进一步的研究来测试在更严重的肥胖中脂肪组织的丧失是否有益。