Department of Endocrinology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Endocrinology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
J Pharmacol Exp Ther. 2021 May;377(2):254-264. doi: 10.1124/jpet.120.000410. Epub 2021 Mar 3.
Bariatric surgery is the most common and effective treatment of severe obesity; however, these bariatric procedures always result in detrimental effects on bone metabolism by underlying mechanisms. This study aims to investigate the skeletal response to bariatric surgery and to explore whether alleviates gut microbiota alteration-induced bone loss after bariatric surgery. Consequently, male SD rats received Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) surgery, respectively, followed by body weight recording. The bone loss after bariatric surgery was further determined by dual-energy X-ray absorptiometry (DXA), micro-CT measurement, histologic analyses, and Western blot. Besides, 16S rDNA gene sequencing was performed to determine the gut microbiota alteration after surgery, and intervention with fecal microbiota from RYGB donor was conducted in obese SD rats, followed by administration. Accordingly, rats in the RYGB and SG groups maintained sustained weight loss, and DXA and micro-CT measurement further demonstrated significant bone loss after bariatric surgery. Besides, histologic and Western blot analyses validated enhanced osteoclastogenesis and inhibited osteoblastogenesis and defective autophagy after surgery. The 16S rDNA gene sequencing suggested a significant alteration of gut microbiota composition in the RYGB group, and intervention with fecal microbiota from RYGB donor further determined that this kind of alteration contributed to the bone loss after RYGB. Meanwhile, might protect against this postoperative bone loss by promoting osteoblast autophagy. In summary, this study suggests novel mechanisms to clarify the skeletal response to bariatric surgery and provides a potential candidate for the treatment of bone disorder among bariatric patients. SIGNIFICANCE STATEMENT: The significance of this study is the discovery of obvious bone loss and defective autophagy after bariatric surgery. Besides, it is revealed that gut microbiota alterations could be the reason for impaired bone mass after bariatric surgery. Furthermore, could alleviate the gut microbiota alteration-induced bone loss after bariatric surgery by promoting osteoblast autophagy.
减重手术是治疗严重肥胖症最常用和最有效的方法；然而，这些减重手术总是通过潜在的机制对骨代谢产生不利影响。本研究旨在探讨减重手术后的骨骼反应，并探讨是否可以减轻减重手术后肠道微生物群改变引起的骨丢失。因此，雄性 SD 大鼠分别接受 Roux-en-Y 胃旁路术（RYGB）和袖状胃切除术（SG）手术，随后记录体重。通过双能 X 射线吸收法（DXA）、微 CT 测量、组织学分析和 Western blot 进一步确定减重手术后的骨丢失。此外，进行 16S rDNA 基因测序以确定手术后肠道微生物群的改变，并在肥胖 SD 大鼠中进行来自 RYGB 供体粪便微生物群的干预，随后进行 给药。结果，RYGB 和 SG 组大鼠持续保持体重减轻，DXA 和微 CT 测量进一步证实减重手术后骨量明显减少。此外，组织学和 Western blot 分析验证了手术后破骨细胞生成增强、成骨细胞生成受抑制和自噬缺陷。16S rDNA 基因测序表明 RYGB 组肠道微生物群组成发生显著改变，来自 RYGB 供体的粪便微生物群干预进一步确定这种改变导致 RYGB 后骨丢失。同时，可能通过促进成骨细胞自噬来预防这种术后骨丢失。综上所述，本研究提出了新的机制来阐明减重手术对骨骼的反应，并为治疗肥胖患者的骨骼疾病提供了一种潜在的候选药物。
