Treatment with an inhibitor of fatty acid synthase attenuates bone loss in ovariectomized mice
Treatment with an inhibitor of fatty acid synthase attenuates bone loss in ovariectomized mice
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DOI：
10.1016/j.bone.2019.02.017
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发表时间：
2019-05-01
期刊：
影响因子：
4.1
通讯作者：
Duque, Gustavo
中科院分区：
文献类型：
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作者：
Bermeo, Sandra;Al Saedi, Ahmed;Duque, Gustavo
骨细胞和脂肪细胞具有拮抗关系。脂肪细胞通过分泌脂肪酸对体外培养的骨细胞产生毒性作用，脂肪酸由脂肪酸合成酶（FAS）合成。体外抑制FAS可使成骨细胞免于脂肪诱导的毒性和细胞死亡。在这项研究中，我们假设FAS抑制将减轻卵巢切除（OVX）小鼠的骨量丢失。我们用浅蓝菌素（一种已知的FAS抑制剂）处理OVX C57 BL/6小鼠6周，并将其骨表型与溶剂处理的对照组进行比较。浅蓝菌素处理的小鼠表现出体重、甘油三酯、瘦素、骨髓和皮下脂肪的显著降低，而血清葡萄糖或促钙激素没有变化。与溶剂处理的OVX组相比，浅蓝菌素处理的OVX组的这些作用与骨丢失的衰减和骨表型的正常化相关。我们的研究结果表明，抑制FAS可促进骨形成，诱导成骨细胞和破骨细胞之间的解偶联，并有利于矿化，从而提供证据表明，抑制FAS可能构成一种新的骨质疏松症的合成代谢疗法。
Bone and fat cells have an antagonistic relationship. Adipocytes exert a toxic effect on bone cells in vitro through the secretion of fatty acids, which are synthesized by fatty acid synthase (FAS). Inhibition of FAS in vitro rescues osteoblasts from fat-induced toxicity and cell death. In this study, we hypothesized that FAS inhibition would mitigate the loss of bone mass in ovariectomized (OVX) mice. We treated OVX C57BL/6 mice with cerulenin (a known inhibitor of FAS) for 6 weeks and compared their bone phenotype with vehicle-treated controls. Cerulenin-treated mice exhibited a significant decrease in body weight, triglycerides, leptin, and marrow and subcutaneous fat without changes in serum glucose or calciotropic hormones. These effects were associated with attenuation of bone loss and normalization of the bone phenotype in the cerulenin-treated OVX group compared to the vehicle-treated OVX group. Our results demonstrate that inhibition of FAS enhances bone formation, induces uncoupling between osteoblasts and osteoclasts, and favors mineralization, thus providing evidence that inhibition of FAS could constitute a new anabolic therapy for osteoporosis.