Microbial metabolites regulate host lipid metabolism through NR5A-Hedgehog signalling.
Microbial metabolites regulate host lipid metabolism through NR5A-Hedgehog signalling.
复制标题
微生物代谢产物通过NR5A - 刺猬（Hedgehog）信号通路调节宿主脂质代谢。
DOI：
10.1038/ncb3515
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发表时间：
2017-05
影响因子：
21.3
通讯作者：
Wang MC
中科院分区：
文献类型：
--
作者：
Lin CJ;Wang MC
微生物与宿主共享相同的环境，微生物代谢分子（代谢物）对宿主生理起着至关重要的作用。环境因素不仅影响寄主微生物的组成，而且调节寄主微生物的代谢。然而，环境、微生物代谢物和宿主代谢之间的确切分子关系在很大程度上仍然未知。本研究发现，环境蛋氨酸通过NR5A核受体和hedgehog信号的内分泌串扰调节秀丽隐杆线虫的细菌甲基代谢，从而调节宿主线粒体动力学和脂质代谢。我们发现，细菌培养基中蛋氨酸缺乏会减少秀丽隐杆线虫合成磷脂酰胆碱所必需的细菌代谢物的产生。二十一烷酰和二脲酰磷脂酰胆碱的减少减弱了NR5A核受体/ nrr -25介导的对刺猬样蛋白/GRL-21的转录抑制。因此，GRL-21的诱导非自主地抑制了Patched受体/PTR-24细胞，导致线粒体断裂和脂质积累。总之，我们的工作揭示了调节宿主线粒体动力学和脂质代谢的环境-微生物-宿主代谢轴，并发现了NR5A-Hedgehog细胞间信号控制这些代谢反应，对宿主的健康和生存具有重要影响。
Microbes and their hosts share the same environment, and microbial metabolic molecules (metabolites) exert crucial effects on host physiology. Environmental factors not only shape the composition of the host’s resident microbes, but also modulate their metabolism. However, the exact molecular relationship among the environment, microbial metabolites and host metabolism remains largely unknown. Here, we discovered that environmental methionine tunes bacterial methyl metabolism to regulate host mitochondrial dynamics and lipid metabolism in Caenorhabditis elegans through an endocrine crosstalk involving NR5A nuclear receptor and hedgehog signaling. We discovered that methionine deficiency in bacterial medium decreases the production of bacterial metabolites that are essential for phosphatidylcholine synthesis in C. elegans. Reductions of diundecanoyl and dilauroyl phosphatidylcholines attenuate NR5A nuclear receptor/NHR-25-mediated transcriptional suppression on the Hedgehog-like protein/GRL-21. The induction of GRL-21 consequently inhibits the Patched receptor/PTR-24 cell non-autonomously, resulting in mitochondrial fragmentation and lipid accumulation. Together, our work reveals an environment-microbe-host metabolic axis regulating host mitochondrial dynamics and lipid metabolism, and discovers NR5A-Hedgehog intercellular signaling that controls these metabolic responses with critical consequences for host health and survival.
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影响因子：
10.5
作者：
Brown JM;Hazen SL
通讯作者：
Hazen SL
DOI：
10.1083/jcb.200905070
发表时间：
2009-08-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rolland SG;Lu Y;David CN;Conradt B
通讯作者：
Conradt B
影响因子：
2.9
作者：
Edwards, Christopher R.;Dang, Weiwei;Berger, Shelley L.
通讯作者：
Berger, Shelley L.
DOI：
10.1126/science.1198719
发表时间：
2011-05-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Muegge BD;Kuczynski J;Knights D;Clemente JC;González A;Fontana L;Henrissat B;Knight R;Gordon JI
通讯作者：
Gordon JI
DOI：
10.1073/pnas.1517448112
发表时间：
2015-10-06
影响因子：
11.1
作者：
Govindan, J. Amaranath;Jayamani, Elamparithi;Ruvkun, Gary
通讯作者：
Ruvkun, Gary