C57BL/6J mice as a polygenic developmental model of diet-induced obesity

Abstract

Susceptibility to obesity changes during the course of life. We utilized theC57BL/6J (B6) and 129S mouse as a genetic model for variation in diet-induced obesity to define the adiposity phenotypes from birth to maturity at8 weeks-of-age. From birth to 8 weeks-of-age, both male and female 129Smice had significantly higher fat mass and adiposity index than B6 mice,although they were not obese. After 8 weeks-of-age, B6 had greater adiposity/obesity than 129S mice in response to a high fat (HF). We sought to deter-mine the mechanism activating the fat accumulation in B6 mice at 8-weeks-of-age. We used microarray analysis of gene expression during developmentof inguinal fat to show that molecular networks of lipogenesis were maximallyexpressed at 8 weeks-of-age. In addition, the DNA methylation analysis of theSfrp5promoter and binding of acetylated histones toSfrp5andAclypromoterregions showed that major differences in the expression of genes of lipogenesisand chromatin structure occur during development. Differences in lipogenesisnetworks could account for the strain-dependent differences in adiposity upto 8 weeks-of-age; however, changes in the expression of genes in these net-works were not associated with the susceptibility to DIO in B6 male micebeyond 8 weeks-of-age.