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

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.