Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss.
Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss.
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DOI：
10.1038/s41467-017-02490-4
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发表时间：
2018-01-04
影响因子：
16.6
通讯作者：
Zaiss MM
中科院分区：
文献类型：
--
作者：
Lucas S;Omata Y;Hofmann J;Böttcher M;Iljazovic A;Sarter K;Albrecht O;Schulz O;Krishnacoumar B;Krönke G;Herrmann M;Mougiakakos D;Strowig T;Schett G;Zaiss MM
已知微生物代谢物可调节宿主的免疫反应。肠道内膳食纤维微生物发酵产生的主要代谢产物短链脂肪酸(SCFA)会影响局部和全身免疫功能。在此，我们发现SCFA是体内破骨细胞代谢和骨量的调节因子。用SCFA治疗小鼠，并用高纤维饮食喂养，显著增加骨量，防止绝经后和炎症引起的骨丢失。SCFA对骨量的保护作用与其抑制破骨细胞分化和体内骨吸收有关，但不影响骨形成。在机制上，丙酸(C3)和丁酸(C4)诱导破骨细胞代谢重编程，导致糖酵解增强，而氧化磷酸化为代价，从而下调必要的破骨细胞基因，如TRAF6和NFATc1。综上所述，这些数据证实SCFA是破骨细胞新陈代谢和骨稳态的有力调节者。短链脂肪酸(SCFA)是肠道内膳食纤维发酵产生的一类主要代谢物。在这里，作者表明，饮食中给予SCFA与抑制小鼠破骨细胞分化、增加骨量和减少病理性骨丢失有关。
Microbial metabolites are known to modulate immune responses of the host. The main metabolites derived from microbial fermentation of dietary fibers in the intestine, short-chain fatty acids (SCFA), affect local and systemic immune functions. Here we show that SCFA are regulators of osteoclast metabolism and bone mass in vivo. Treatment of mice with SCFA as well as feeding with a high-fiber diet significantly increases bone mass and prevents postmenopausal and inflammation-induced bone loss. The protective effects of SCFA on bone mass are associated with inhibition of osteoclast differentiation and bone resorption in vitro and in vivo, while bone formation is not affected. Mechanistically, propionate (C3) and butyrate (C4) induce metabolic reprogramming of osteoclasts resulting in enhanced glycolysis at the expense of oxidative phosphorylation, thereby downregulating essential osteoclast genes such as TRAF6 and NFATc1. In summary, these data identify SCFA as potent regulators of osteoclast metabolism and bone homeostasis. Short-chain fatty acids (SCFA) are a main class of metabolites derived from fermentation of dietary fibre in the intestine. Here, the authors show that dietary administration of SCFA is associated with inhibition of osteoclast differentiation, increased bone mass, and reduced pathological bone loss in mice.
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DOI：
10.1016/j.berh.2014.10.018
发表时间：
2014-10
期刊：
Best practice & research. Clinical rheumatology
影响因子：
--
作者：
Asquith M;Elewaut D;Lin P;Rosenbaum JT
通讯作者：
Rosenbaum JT
影响因子：
15.9
作者：
Li, Jau-Yi;Chassaing, Benoit;Pacifici, Roberto
通讯作者：
Pacifici, Roberto
影响因子：
15.9
作者：
Abdollahi-Roodsaz, Shahla;Joosten, Leo A. B.;Van den Berg, Wim B.
通讯作者：
Van den Berg, Wim B.
影响因子：
4.3
作者：
McCabe L;Britton RA;Parameswaran N
通讯作者：
Parameswaran N
DOI：
10.1084/jem.20151570
发表时间：
2016-01-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
O'Neill LA;Pearce EJ
通讯作者：
Pearce EJ