The Impact of Acute Caloric Restriction on the Metabolic Phenotype in Male C57BL/6 and DBA/2 Mice

Caloric restriction (CR) extends healthy lifespan in many organisms. DBA/2 mice, unlike C57BL/6 mice, are reported to be unresponsive to CR. To investigate potential differences underlying the CR response in male DBA/2 and C57BL/6 mice, we examined several metabolic parameters following acute (1-5 weeks) 30% CR. Acute CR decreased body mass (BM) in both strains, with lean and fat mass decreasing in proportion to BM. Resting metabolic rate (RMR) was unaltered by CR, following appropriate corrections for BM differences, although RMR was higher in DBA/2 compared to C57BL/6 mice. Acute CR decreased fed blood glucose levels in both strains, decreased fasting blood glucose in C57BL/6 mice but increased fasting levels in DBA/2 mice. Glucose tolerance improved after 1 week of CR in C57BL/6 mice but improved only after 4 weeks in DBA/2 mice. Acute CR had no effect on insulin levels, but lowered insulin sensitivity and decreased insulin-like growth factor-1 (IGF-1) levels in both strains. DBA/2 mice were hyperinsulinaemic and insulin resistant compared to C57BL/6 mice. These strain-specific differences in glucose homeostatic parameters may underlie the reported unresponsiveness of DBA/2 mice to CR. We also demonstrate delineation in the response of insulin and IGF-1 to acute CR in mice.