Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
Department of Orthopedic Surgery, and Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affifiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Jul 10;14:1171781. doi: 10.3389/fendo.2023.1171781. eCollection 2023.
The current study aimed to investigate the pathogenesis of obesity-induced impaired bone mass accrual and the impact of dietary intervention on bone density in the mouse model of obesity.
Mice were fed with chow diet (CD) for 10 months, high-fat-diet (HFD) for 10 months, or HFD for 6 months then transferred to chow diet for 4 months (HFDt).
Weight loss and decreased intrahepatic lipid accumulation were observed in mice following dietary intervention. Additionally, HFD feeding induced bone mass accrual, while diet intervention restrained trabecular bone density. These changes were further reflected by increased osteogenesis and decreased adipogenesis in HFDt mice compared to HFD mice. Furthermore, HFD feeding decreased the activity of the Wingless-related integration site (Wnt)-β-Catenin signaling pathway, while the Wnt signaling was augmented by diet intervention in the HFDt group.
Our findings suggest that a HFD inhibits bone formation and that dietary intervention reverses this inhibition. Furthermore, the dietary intervention was able to compensate for the suppressed increase in bone mass to a level comparable to that in the CD group. Our study suggests that targeting the Wnt signaling pathway may be a potential approach to treat obesity-induced impaired bone mass accrual.
本研究旨在探讨肥胖导致骨量积累受损的发病机制，以及饮食干预对肥胖小鼠模型骨密度的影响。
将小鼠分别用标准饮食（CD）喂养 10 个月、高脂饮食（HFD）喂养 10 个月或 HFD 喂养 6 个月后转换为 CD 喂养 4 个月（HFDt）。
饮食干预后，小鼠体重减轻，肝内脂质蓄积减少。此外，HFD 喂养诱导骨量增加，而饮食干预则抑制了小梁骨密度。与 HFD 组相比，HFDt 组的成骨作用增强，脂肪生成减少，进一步反映了这些变化。此外，HFD 喂养降低了 Wnt-β-连环蛋白信号通路的活性，而饮食干预则增强了 HFDt 组的 Wnt 信号。
我们的研究结果表明，HFD 抑制骨形成，而饮食干预则逆转了这种抑制作用。此外，饮食干预能够补偿骨量增加的抑制，使其达到与 CD 组相当的水平。我们的研究表明，靶向 Wnt 信号通路可能是治疗肥胖导致骨量减少的一种潜在方法。
