Metabolic Profiling Reveals a Contribution of Gut Microbiota to Fatty Liver Phenotype in Insulin-Resistant Mice

Here, we study the intricate relationship between gut microbiota and host cometabolic phenotypes associated with dietary-induced impaired glucose homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain (12956) known to be susceptible to these disease traits, using plasma and urine...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-08, Vol.103 (33), p.12511-12516
Main Authors: Dumas, Marc-Emmanuel, Barton, Richard H., Toye, Ayo, Cloarec, Olivier, Blancher, Christine, Rothwell, Alice, Fearnside, Jane, Tatoud, Roger, Blanc, Véronique, Lindon, John C., Mitchell, Steve C., Holmes, Elaine, McCarthy, Mark I., Scott, James, Gauguier, Dominique, Nicholson, Jeremy K.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Body Weight
Dietary Fats
Energy metabolism
Excretion
Fatty Liver - physiopathology
Gastrointestinal Tract - microbiology
Genetics
Genotype & phenotype
Glucose - metabolism
Homeostasis
Insulin
Insulin - metabolism
Insulin resistance
Insulin Resistance - physiology
Lipid metabolism
Lipids - blood
Liver
Liver - anatomy & histology
Liver - metabolism
Liver diseases
Male
Metabolism
Methylamines
Methylamines - blood
Methylamines - urine
Mice
Mice, Inbred BALB C
Microbiota
Microorganisms
Multivariate Analysis
Nuclear Magnetic Resonance, Biomolecular
Phenotype
Rodents
Urine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Here, we study the intricate relationship between gut microbiota and host cometabolic phenotypes associated with dietary-induced impaired glucose homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain (12956) known to be susceptible to these disease traits, using plasma and urine metabotyping, achieved by 1H NMR spectroscopy. Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 12956 mouse to impaired glucose homeostasis and NAFLD is associated with disruptions of choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine and high urinary excretion of methylamines (dimethylamine, trimethylamine, and trimethylamine-Noxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiota in strain 12956 on a high-fat diet reduces the bioavailability of choline and mimics the effect of choline-deficient diets, causing NAFLD. These data also indicate that gut microbiota may play an active role in the development of insulin resistance.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0601056103