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Physiol. Genomics 39: 172-182, 2009. First published August 11, 2009; doi:10.1152/physiolgenomics.90350.2008
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Received 7 October 2008; accepted in final form 5 August 2009.
Physiological Genomics 39:172-182 (2009)
Copyright © 2009 the American Physiological Society © 2009 American Physiological Society

Call for Papers: Computational Modeling of Physiological Systems

Effects of atherogenic diet on hepatic gene expression across mouse strains

Keith R. Shockley 1, David Witmer 2, Sarah L. Burgess-Herbert 1, Beverly Paigen 1 and Gary A. Churchill 1

1The Jackson Laboratory, Bar Harbor; and
2The Maine School of Science and Mathematics, Limestone, Maine

Diets high in fat and cholesterol are associated with increased obesity and metabolic disease in mice and humans. To study the molecular basis of the metabolic response to dietary fat, 10 inbred strains of mice were fed atherogenic high-fat and control low-fat diets. Liver gene expression and whole animal phenotypes were measured and analyzed in both sexes. The effects of diet, strain, and sex on gene expression were determined irrespective of complex processes, such as feedback mechanisms, that could have mediated the genomic responses. Global gene expression analyses demonstrated that animals of the same strain and sex have similar transcriptional profiles on a low-fat diet, but strains may show considerable variability in response to high-fat diet. Functional profiling indicated that high-fat feeding induced genes in the immune response, indicating liver damage, and repressed cholesterol biosynthesis. The physiological significance of the transcriptional changes was confirmed by a correlation analysis of transcript levels with whole animal phenotypes. The results found here were used to confirm a previously identified quantitative trait locus on chromosome 17 identified in males fed a high-fat diet in two crosses, PERA x DBA/2 and PERA x I/Ln. The gene expression data and phenotype data have been made publicly available as an online tool for exploring the effects of atherogenic diet in inbred mouse strains (http://cgd-array.jax.org/DietStrainSurvey).

dietary fat; liver; microarray analysis; obesity; strain survey




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