The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice

被引：0

作者：

Alida Kindt

Gerhard Liebisch

Thomas Clavel

Dirk Haller

Gabriele Hörmannsperger

Hongsup Yoon

Daniela Kolmeder

Alexander Sigruener

Sabrina Krautbauer

Claudine Seeliger

Alexandra Ganzha

Sabine Schweizer

Rosalie Morisset

Till Strowig

Hannelore Daniel

Dominic Helm

Bernhard Küster

Jan Krumsiek

Josef Ecker

机构：

[1] Helmholtz Zentrum München,Institute of Computational Biology

[2] Universitätsklinikum Regensburg,Institute of Clinical Chemistry

[3] Universitätsklinikum Aachen,Functional Microbiome Research Group, Institute of Medical Microbiology

[4] Technische Universität München (TUM),ZIEL Institute for Food and Health

[5] Technische Universität München (TUM),Ernährung und Immunologie

[6] Technische Universität München (TUM),Ernährungsphysiologie

[7] Helmholtz Centre for Infection Research,Research Group Microbial Immune Regulation

[8] Technische Universität München (TUM),Proteomics and Bioanalytics

[9] German Center for Diabetes Research (DZD),Department of Analytical Biosciences, Leiden Academic Centre for Drug Research

[10] Leiden University,undefined

[11] Institute for Computational Biomedicine,undefined

[12] Englander Institute for Precision Medicine,undefined

[13] Department of Physiology and Biophysics,undefined

[14] Weill Cornell Medicine,undefined

来源：

Nature Communications | / 9卷

关键词：

D O I：

暂无

中图分类号：

学科分类号：

摘要：

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.

引用

共 189 条

[1] Sekirov I(2010)Gut microbiota in health and disease Physiol. Rev. 90 859-904
[2] Russell SL(2014)Specialized metabolites from the microbiome in health and disease Cell. Metab. 20 719-730
[3] Antunes LC(2011)Programming of host metabolism by the gut microbiota Ann. Nutr. Metab. 58 44-52
[4] Finlay BB(2008)Membrane lipids: where they are and how they behave Nat. Rev. Mol. Cell Biol. 9 112-124
[5] Sharon G(2008)The opposing effects of n-3 and n-6 fatty acids Prog. Lipid Res. 47 147-155
[6] Backhed F(2016)Homeoviscous adaptation and the regulation of membrane lipids J. Mol. Biol. 428 4776-4791
[7] van Meer G(2014)Lipid cell biology. Polyunsaturated phospholipids facilitate membrane deformation and fission by endocytic proteins Science 345 693-697
[8] Voelker DR(2010)Lipidomics: new tools and applications Cell 143 888-895
[9] Feigenson GW(2010)Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes Proc. Natl. Acad. Sci. USA 107 7817-7822
[10] Schmitz G(2003)Structural and functional organization of the animal fatty acid synthase Prog. Lipid Res. 42 289-317

← 1 2 3 4 5 6 7 8 9 10 →