The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice.
The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice.
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DOI：
10.1038/s41467-018-05767-4
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发表时间：
2018-09-14
影响因子：
16.6
通讯作者：
Ecker J
中科院分区：
文献类型：
--
作者：
Kindt A;Liebisch G;Clavel T;Haller D;Hörmannsperger G;Yoon H;Kolmeder D;Sigruener A;Krautbauer S;Seeliger C;Ganzha A;Schweizer S;Morisset R;Strowig T;Daniel H;Helm D;Küster B;Krumsiek J;Ecker J
肠道微生物生态系统与宿主脂质平衡之间的相互作用与宿主生理和代谢疾病密切相关。我们提出了一个全面的多组学的观点，肠道微生物定植对肝脏脂质代谢的影响，整合转录组学，蛋白质组学，磷酸蛋白质组学和脂质组学分析的肝脏和血浆样品的无菌和特定病原体无小鼠。微生物通过硬脂酰辅酶A去饱和酶1诱导单不饱和脂肪酸产生，通过脂肪酸延长酶5诱导多不饱和脂肪酸延长，导致甘油磷脂酰基链谱的显著改变。根据无菌小鼠脂肪酸谱的观察到的变化计算的复合分类评分清楚地区分了具有高灵敏度的抗疟治疗的小鼠和未治疗的对照小鼠。机制研究表明，源自膳食纤维的肠道微生物降解的乙酸盐可作为C16和C18脂肪酸及其相关甘油磷脂物质的肝脏合成的前体，这些脂肪酸及其相关甘油磷脂物质也被释放到循环中。肠道微生物群在肝脏脂质代谢中的作用是有争议的，也不完全清楚。在这里，作者对无菌和无特定病原体小鼠的脂质代谢过程进行了多组学分析，揭示了肠道微生物群如何影响肝脏脂肪酸去饱和和延长。
Interactions between the gut microbial ecosystem and host lipid homeostasis are highly relevant to host physiology and metabolic diseases. We present a comprehensive multi-omics view of the effect of intestinal microbial colonization on hepatic lipid metabolism, integrating transcriptomic, proteomic, phosphoproteomic, and lipidomic analyses of liver and plasma samples from germfree and specific pathogen-free mice. Microbes induce monounsaturated fatty acid generation by stearoyl-CoA desaturase 1 and polyunsaturated fatty acid elongation by fatty acid elongase 5, leading to significant alterations in glycerophospholipid acyl-chain profiles. A composite classification score calculated from the observed alterations in fatty acid profiles in germfree mice clearly differentiates antibiotic-treated mice from untreated controls with high sensitivity. Mechanistic investigations reveal that acetate originating from gut microbial degradation of dietary fiber serves as precursor for hepatic synthesis of C16 and C18 fatty acids and their related glycerophospholipid species that are also released into the circulation. The role of the gut microbiota in hepatic lipid metabolism is controversial and incompletely understood. Here the authors perform multi-omics analyses of altered lipid metabolic processes in germ-free and specific pathogen-free mice, revealing how the gut microbiota affects hepatic fatty acid desaturation and elongation.
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影响因子：
4.4
作者：
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通讯作者：
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3.7
作者：
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5.8
作者：
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通讯作者：
Wright, FA