Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice.
Insulin resistance plays a central role in type 2 diabetes and obesity, which develop as a consequence of genetic and environmental factors. Dietary changes including high fat diet (HFD) feeding promotes insulin resistance in rodent models which present useful systems for studying interactions between genetic background and environmental influences contributing to disease susceptibility and progression. We applied a combination of classical physiological, biochemical and hormonal studies and plasma (1)H NMR spectroscopy-based metabonomics to characterize the phenotypic and metabotypic consequences of HFD (40%) feeding in inbred mouse strains (C57BL/6, 129S6, BALB/c, DBA/2, C3H) frequently used in genetic studies. We showed the wide range of phenotypic and metabonomic adaptations to HFD across the five strains and the increased nutrigenomic predisposition of 129S6 and C57BL/6 to insulin resistance and obesity relative to the other strains. In contrast mice of the BALB/c and DBA/2 strains showed relative resistance to HFD-induced glucose intolerance and obesity. Hierarchical metabonomic clustering derived from (1)H NMR spectral data of the strains provided a phylometabonomic classification of strain-specific metabolic features and differential responses to HFD which closely match SNP-based phylogenetic relationships between strains. Our results support the concept of genomic clustering of functionally related genes and provide important information for defining biological markers predicting spontaneous susceptibility to insulin resistance and pathological adaptations to fat feeding.
Fearnside
Jane F
JF
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Dumas
Marc-Emmanuel
ME
Rothwell
Alice R
AR
Wilder
Steven P
SP
Cloarec
Olivier
O
Toye
Ayo
A
Blancher
Christine
C
Holmes
Elaine
E
Tatoud
Roger
R
Barton
Richard H
RH
Scott
James
J
Nicholson
Jeremy K
JK
Gauguier
Dominique
D
D000222:Adaptation, Physiological; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D007333:Insulin Resistance; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008660:Metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity; D010641:Phenotype; D010802:Phylogeny; D013045:Species Specificity
D004041:Dietary Fats