Comparison of low-fat and high-fat diet on gene expression in muscle, liver and adipose tissue from mice of two genetic backgrounds

Diet-induced obesity is the primary determinant of the current epidemic of diabetes. We have explored the role of genetics in this phenomenon, using C57Bl/6 (B6) and 129S6/SvEvTac (129) mice on a low- or high-fat diet. Microarray analysis indicated significant changes in expression levels between B6 and 129 mice in the chromosomal area of Wnt5a and protein kinase C delta (PKC-delta). Thus, caloric efficiency, i.e., the “thrifty gene,” is a dominant-acting genetic determinant of diet-induced obesity in mice and can be linked to a locus on chromosome 14, including genes linked to adipose development and insulin sensitivity. Skeletal muscle, liver, and epididymal fat pads were removed from B6 and 129 mice at the age of 6 months after the mice were maintained on a standard diet that contained 21% of calories from fat, 22% from protein, and 57% from carbohydrates. A total of 25 ug RNA pooled from two to three mice was used for cRNA synthesis and hybridization on Affymetrix microarray chips.