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Identification of genes contributing to the obese yellow A^vy phenotype: caloric restriction, genotype, diet x genotype interactions

¹ University of California at Davis, Davis, California 95616
² Northwestern University Medical School, Chicago, Illinois 60611
³ University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
⁴ Department of Internal Medicine, University of Illinois College of Medicine, Urbana, Illinois 61821
⁵ National Center for Toxicological Research/United States Food and Drug Administration, Jefferson, Arkansas 72079

The incidence and severity of obesity and type 2 diabetes are increasing in Western societies. The progression of obesity to type 2 diabetes is gradual with overlapping symptoms of insulin resistance, hyperinsulinemia, hyperglycemia, dyslipidemias, ion imbalance, and inflammation; this complex syndrome has been called diabesity. We describe here comparisons of gene expression in livers of A/a (agouti) vs. A^vy/A (obese yellow) segregants (i.e., littermates) from BALB/cStCrlfC3H/Nctr x VYWffC3Hf/Nctr-A^vy/a matings in response to 70% and 100% of ad libitum caloric intakes of a reproducible diet. Twenty-eight (28) genes regulated by diet, genotype, or diet x genotype interactions mapped to diabesity quantitative trait loci. A subset of the identified genes is linked to abnormal physiological signs observed in obesity and diabetes.

gene regulation; diabetes; obesity; diabesity; quantitative trait locus; expression

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