Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies.
Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging C57BL/6 mice and in vitro studies.
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DOI：
10.1038/s41598-021-89827-8
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发表时间：
2021-05-14
影响因子：
4.6
通讯作者：
Rahman MM
中科院分区：
文献类型：
--
作者：
Cugno C;Kizhakayil D;Calzone R;Rahman SM;Halade GV;Rahman MM
罗格列酮是一种有效的胰岛素增敏剂，但与骨质流失相关，主要是由于骨吸收增加和骨髓肥胖所致。我们研究了同时服用富含 omega-3 脂肪酸 (FA) 的鱼油对 C57BL/6 小鼠罗格列酮诱导的骨质流失的影响以及潜在预防作用的机制。与其他组相比，喂食添加鱼油的等热量饮食的小鼠在不同区域表现出显着更高的骨密度水平。在同一组小鼠中，观察到 COX-2 活性降低，碱性磷酸酶活性增强，组织蛋白酶 k、PPAR-γ 和促炎细胞因子水平降低，抗炎细胞因子水平升高。此外，鱼油可恢复罗格列酮诱导的C3H10T1/2细胞中成骨细胞分化的下调和脂肪细胞分化的上调，并抑制RANKL处理的RAW264.7细胞中破骨细胞分化的上调。我们最终测试了我们对分化为骨细胞和脂肪细胞的人间充质基质细胞的假设，证实了二十二碳六烯酸（DHA）omega-3 FA在罗格列酮治疗期间的有益作用，通过下调脂肪形成基因，例如沿着PPARγ/FABP4轴的adipsin和FABP4，并降低脂肪生成基因的能力 骨细胞转向脂肪生成。鱼油可以通过抑制炎症、破骨细胞生成和脂肪生成以及增强骨微环境中的成骨来防止罗格列酮引起的骨质流失。
Rosiglitazone is an effective insulin-sensitizer, however associated with bone loss mainly due to increased bone resorption and bone marrow adiposity. We investigated the effect of the co-administration of fish oil rich in omega-3 fatty acids (FAs) on rosiglitazone-induced bone loss in C57BL/6 mice and the mechanisms underlying potential preventive effect. Mice fed the iso-caloric diet supplemented with fish oil exhibited significantly higher levels of bone density in different regions compared to the other groups. In the same cohort of mice, reduced activity of COX-2, enhanced activity of alkaline phosphatase, lower levels of cathepsin k, PPAR-γ, and pro-inflammatory cytokines, and a higher level of anti-inflammatory cytokines were observed. Moreover, fish oil restored rosiglitazone-induced down-regulation of osteoblast differentiation and up-regulation of adipocyte differentiation in C3H10T1/2 cells and inhibited the up-regulation of osteoclast differentiation of RANKL-treated RAW264.7 cells. We finally tested our hypothesis on human Mesenchymal Stromal Cells differentiated to osteocytes and adipocytes confirming the beneficial effect of docosahexaenoic acid (DHA) omega-3 FA during treatment with rosiglitazone, through the down-regulation of adipogenic genes, such as adipsin and FABP4 along the PPARγ/FABP4 axis, and reducing the capability of osteocytes to switch toward adipogenesis. Fish oil may prevent rosiglitazone-induced bone loss by inhibiting inflammation, osteoclastogenesis, and adipogenesis and by enhancing osteogenesis in the bone microenvironment.
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影响因子：
4.8
作者：
Ali, AA;Weinstein, RS;Jilka, RL
通讯作者：
Jilka, RL
影响因子：
6.1
作者：
Echeverria, Francisca;Valenzuela, Rodrigo;Videla, Luis A.
通讯作者：
Videla, Luis A.
影响因子：
168.9
作者：
Dormandy, JA;Charbonnel, B;Taton, J
通讯作者：
Taton, J
影响因子：
5.6
作者：
Bhattacharya, Arunabh;Sun, Dongxu;Fernandes, Gabriel
通讯作者：
Fernandes, Gabriel
DOI：
10.1016/j.plefa.2016.10.001
发表时间：
2016-11-01
影响因子：
3
作者：
Echeverria, Francisca;Ortiz, Macarena;Videla, Luis A.
通讯作者：
Videla, Luis A.