Changes in gene expression foreshadow diet-induced obesity in genetically identical mice.

Robert Koza, Larissa Nikonova, Jessica Hogan, Jong-Seop Rim, Tamra Mendoza, Christopher Faulk, Jihad Skaf and Leslie Kozak

PLOS Genetics 2006. 2: e81.


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.

Our Thoughts on This Paper

We recently discussed the paper Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice. We were interested in this paper because our lab is searching for new, effective ways to describe patients who are at-risk obesity. Koza et al. placed C57BL/6J mice on a 60% high fat diet and analyzed gene expression regarding adiposity in the top 10% of weight gainers and the bottom 10% of weight gainers. The group concluded that mice within the “high gainer” category were more metabolically efficient when turning calories into body mass, leading to more food consumption. Using microarray analysis, they identified several genes (SRFP5, Naked1, BMP3, MEST) responsible for reversing the inhibition of adipogenesis, which are elevated at before the start of high fat diet in “high gainers” (as compared to “low gainers”). They propose that these genes are stable within a mouse and predispose it to weight gain independent of the diet. It would be very interesting to look at possible other factors that are causing this predisposition to obesity.

Written by Matthew Peloquin on May 13, 2014.


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