Changes in gene expression foreshadow diet-induced obesity in genetically identical mice.
High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet) correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity.
Koza
Robert A
RA
Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Nikonova
Larissa
L
Hogan
Jessica
J
Rim
Jong-Seop
JS
Mendoza
Tamra
T
Faulk
Christopher
C
Skaf
Jihad
J
Kozak
Leslie P
LP
D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue; D000821:Animal Feed; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D036341:Intercellular Signaling Peptides and Proteins; C487972:Sfrp5 protein, mouse; D000094742:Secreted Frizzled-Related Proteins