Calorie restriction (CR) is an effective intervention to prevent chronic diseases including cancer. Although many factors, i.e., sex hormones, IGF-I and mTOR have been studied in response to CR, the molecular mechanisms of CR remain to be identified. Our objective was to determine the short and long-term effects of different CR protocols on pro-inflammatory cytokines. Our hypothesis was that Intermittent CR (ICR) would result in greater inhibition of pro-inflammatory serum cytokines compared to Chronic CR (CCR) as we previously found ICR to be more protective in the prevention of mammary tumor development. From ten weeks of age female C57BL6 mice were maintained on either ad libitum (AL) fed, ICR or CCR protocols (overall CR of ~ 75% of AL) for up to 74 weeks of age. Blood samples were collected for measurements of serum interleukin-6 (IL-6), tumor necrosis factor–alpha (TNF-α), adiponectin, leptin, IGF-I and insulin at specified ages. For ICR mice samples were collected following 3 weeks of restriction (ICR-R) and after one week of refeeding (ICR-RF). In general, both modes of CR significantly reduced serum IL-6, TNF-α, IGF-I and leptin levels compared to AL with IL-6 levels 24 and 3.5 fold and TNF-α levels t 11 and 1.5 fold lower in ICR and CCR groups, respectively at study termination. There was a trend for adiponectin and insulin to be highest in ICR-RF mice. Body weights were positively correlated with IL-6, TNF-α, insulin and leptin but negatively correlated with adiponectin-to-leptin ratio. Moreover, there was a positive correlation between IL-6 and TNF-α. Beneficial effects of ICR may function through pro-inflammatory cytokine pathways.
Bibliographical noteFunding Information:
This work was supported by the grants CA101858, CA157012, The Breast Cancer Research Foundation and The Hormel Foundation. The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific research.
- Calorie restriction
- Wild-type mice