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.
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.


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.


CONCLUSIONS
Cancer prevention efforts based on CR and down-regulation of the IGF-1 pathway will require consideration of deleterious effects on bone.
Berrigan
David
D
Applied Research Program. Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892, USA. berrigad@mail.nih.gov
Lavigne
Jackie A
JA
Perkins
Susan N
SN
Nagy
Tim R
TR
Barrett
J Carl
JC
Hursting
Stephen D
SD
D015502:Absorptiometry, Photon; D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D031204:Caloric Restriction; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D002149:Energy Intake; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000517:prevention & control*; D010641:Phenotype
D007334:Insulin-Like Growth Factor I