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

Full Abstract

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.

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Author information

Author/s: Koza, Robert A (RA); Nikonova, Larissa (L); Hogan, Jessica (J); Rim, Jong-Seop (JS); Mendoza, Tamra (T); Faulk, Christopher (C); Skaf, Jihad (J); Kozak, Leslie P (LP);

Affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

Grants: P-30 DK072476 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: PLoS genetics (PLoS Genet), published in United States. (Language: eng)

Reference: 2006-May; vol 2 (issue 5) : pp e81

Dates: Created 2006/05/30; Completed 2006/07/31; Revised 2008/11/20;

PMID: 16733553, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Feeding Behavior
Gene Expression Regulation
Intercellular Signaling Peptides and Proteins - genetics
Male
Mice
Mice, Inbred C57BL
Obesity - genetics; pathology
Phenotype

Associated Chemicals: Intercellular Signaling Peptides and Proteins (0) ; Sfrp5 protein, mouse (0)

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