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

ABSTRACT: 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 induced 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. Germfree mice contained more abundant saturated and poly-unsaturated lipids, whereas colonized mice primarily contained mono-unsaturated lipids. A composite classification score calculated from the observed alterations in fatty acid profiles in germfree mice clearly differentiated antibiotic-treated mice from untreated controls with high sensitivity. Mechanistic investigations revealed 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

DISEASE(S): Disease Free

SUBMITTER: Dominic Helm  

LAB HEAD: Josef Ecker

PROVIDER: PXD010412 | Pride | 2018-07-20

REPOSITORIES: Pride