The protective effect of intermittent calorie restriction on mammary tumorigenesis is not compromised by consumption of a high fat diet during refeeding
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Previously we reported that intermittent calorie restriction (ICR) provided greater prevention of mammary tumors (MTs) than chronic calorie restriction (CCR). Here the impact of increased fat intake during refeeding in an ICR protocol was evaluated. MMTV-TGF-α female mice were assigned to one of three groups: ad libitum (AL) fed (n = 45) with free access to a moderately high fat diet (22 % fat calories); ICR (n = 45) 50 % calorie restricted for 3-week intervals followed by 3 weeks of 100 % of AL intake; and CCR (n = 45) fed 75 % of AL mice, matching each 6-week cycle of ICR mice. ICR mice were further designated as ICR-Restricted or ICR-Refed for data obtained during these intervals. All mice consumed the same absolute amount of dietary fat. Mice were followed to assess MT incidence, body weight and serum IGF-1, IGFBP3, leptin and adiponectin levels until 79 (end of final 3-week restriction) or 82 (end of final 3-weeks refeeding) weeks of age. Age of MT detection was significantly extended for CCR (74 weeks) and ICR (82 weeks) mice, compared to 57.5 weeks for AL mice. MT incidence for AL, ICR and CCR mice was 66.7, 4.4, and 52.3 %, respectively. Mammary and fat pad weights were reduced significantly following 50 % calorie restriction in ICR-Restricted mice compared to AL, CCR and ICR-Refed mice. IGF-1 and leptin levels also tended to be reduced in ICR-Restricted mice over the course of the study while adiponectin was not compared to AL, CCR, and ICR-Refed mice. The adiponectin:leptin ratio was consistently higher following 50 % restriction in ICR-Restricted mice. There was no relationship of IGF-1, leptin, or adiponectin with the presence of MTs in any groups. Thus the manner in which calories are restricted impacts the protective effect of calorie restriction independently of high fat intake.
KeywordsCalorie restriction Prevention Tumorigenesis Mammary tumors Breast cancer IGF-1 Leptin Adiponectin Fat intake
Intermittent calorie restriction
Chronic caloric restriction
Insulin-like growth factor-1
Insulin-like growth factor binding protein-3
Mouse mammary tumor virus transforming growth factor-α
This research was supported by NIH-CA 101858 and the Hormel Foundation.
Conflict of interest
We declare that we do not have a financial relationship with the organizations that sponsored the research.
All procedures with mice were performed under the guidelines and with approval of the University of Minnesota Institutional Animal Care and Use Committee. The University of Minnesota is an AAALAC accredited institution.
- 2.Ruggeri BA, Klurfeld DM, Kritchevsky D, Furlanetto RW (1989) Caloric restriction and 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in rats: alterations in circulating insulin, insulin-like growth factors I and II, and epidermal growth factor. Cancer Res 49:4130–4134PubMedGoogle Scholar
- 20.Cleary MP, Jacobson MK, Phillips FC et al (2002) Weight-cycling decreases incidence and increases latency of mammary tumor development to a greater extent than does chronic restriction in mouse mammary tumor virus-transforming growth factor-α female mice. Cancer Epidemiol Biomarkers Prev 11:836–843PubMedGoogle Scholar
- 21.Cleary MP, Hu X, Grossmann ME et al (2007) Prevention of mammary tumorigenesis by intermittent caloric restriction, does caloric intake during refeeding modulate the response? Exp Biol Med. 232:70–80Google Scholar
- 41.Shankaraiah K, Halberg F, Yunis E, Watson LM (1984) Alternate-day feeding alters the circadian system, reduces breast cancer incidence and prolongs life. In: Halberg F, Reale L, Tarquini B (eds) Proceedings of II international symposium on chronobiologic approach to social medicine. Instituto Itaniano di Medicina Sociale, Rome, pp 633–648Google Scholar
- 60.Cleary MP, Ray A, Rogozina OP et al (2009) Targeting the adiponectin-leptin ratio for prevention of postmenopausal breast cancer. Front Biosci 1:329–357Google Scholar