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The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice.
Kindt, Alida Liebisch, Gerhard Clavel, Thomas Haller, Dirk Hörmannsperger, Gabriele Yoon, Hongsup Kolmeder, Daniela Sigruener, Alexander Krautbauer, Sabrina Seeliger, Claudine
Kindt, Alida
Liebisch, Gerhard
Clavel, Thomas
Haller, Dirk
Hörmannsperger, Gabriele
Yoon, Hongsup
Kolmeder, Daniela
Sigruener, Alexander
Krautbauer, Sabrina
Seeliger, Claudine
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2018-09-14
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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.
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2041-1723
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Attribution-NonCommercial-ShareAlike 3.0 United States