TY - JOUR
T1 - Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice
AU - Dumas, Marc Emmanuel
AU - Barton, Richard H.
AU - Toye, Ayo
AU - Cloarec, Olivier
AU - Blancher, Christine
AU - Rothwell, Alice
AU - Fearnside, Jane
AU - Tatoud, Roger
AU - Blanc, Véronique
AU - Lindon, John C.
AU - Mitchell, Steve C.
AU - Holmes, Elaine
AU - McCarthy, Mark I.
AU - Scott, James
AU - Gauguier, Dominique
AU - Nicholson, Jeremy K.
PY - 2006/8/15
Y1 - 2006/8/15
N2 - 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 1H 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.
AB - 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 1H 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.
KW - Metabolic syndrome
KW - Metabonomics NMR
KW - Nonalcoholic fatty liver disease
KW - Nutritional genomics
UR - http://www.scopus.com/inward/record.url?scp=33747618036&partnerID=8YFLogxK
U2 - 10.1073/pnas.0601056103
DO - 10.1073/pnas.0601056103
M3 - Article
C2 - 16895997
AN - SCOPUS:33747618036
SN - 0027-8424
VL - 103
SP - 12511
EP - 12516
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 33
ER -