Phenotypic Effects of Calorie Restriction and Insulin-like Growth Factor-1 Treatment on Body Composition and Bone Mineral Density of C57BL/6 Mice: Implications for Cancer Prevention

Abstract

Background: Calorie restriction (CR) inhibits carcinogenesis and delays aging. Some anti-carcinogenic effects of CR are mediated by decreased circulating insulin-like growth factor-1 (IGF-1); however, IGF-1 also plays an important role in regulating growth and bone density. Materials and Methods: We quantified tradeoffs involving the CR/IGF-1 axis in C57BL/6 mice by examining body composition and bone characteristics in ad libitum fed, 20, 30 or 40% CR mice that received placebo or recombinant murine IGF-1 delivered with a time-release pellet. After 26 days, carcasses were scanned with a PIXImus II dual-energy X-ray absorptiometer. Results: CR reduced body weight and percent body fat and had non-linear effects on bone density. IGF-1 restored bone density to control levels or greater in the CR mice. Conclusion: Cancer prevention efforts based on CR and down-regulation of the IGF-1 pathway will require consideration of deleterious effects on bone.