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 (129S6) known to be susceptible to these disease traits, using plasma and urine metabotyping, achieved by (1)H NMR spectroscopy. Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 129S6 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-N-oxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiota in strain 129S6 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.
Dumas
Marc-Emmanuel
ME
Department of Biological Chemistry, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
Barton
Richard H
RH
Toye
Ayo
A
Cloarec
Olivier
O
Blancher
Christine
C
Rothwell
Alice
A
Fearnside
Jane
J
Tatoud
Roger
R
Blanc
Véronique
V
Lindon
John C
JC
Mitchell
Steve C
SC
Holmes
Elaine
E
McCarthy
Mark I
MI
Scott
James
J
Gauguier
Dominique
D
Nicholson
Jeremy K
JK
D000818:Animals; D001835:Body Weight; D004041:Dietary Fats; D005234:Fatty Liver / Q000503:physiopathology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008297:Male; D008744:Methylamines / Q000097:blood / Q000652:urine; D051379:Mice; D008807:Mice, Inbred BALB C; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular; D010641:Phenotype
D004041:Dietary Fats; D007328:Insulin; D008055:Lipids; D008744:Methylamines; D005947:Glucose