Effects of meal timing on tumor progression in mice

Life Sci. 2004 Jul 23;75(10):1181-93. doi: 10.1016/j.lfs.2004.02.014.

Abstract

Meal timing can reset circadian clocks in peripheral tissues. We investigated the effects of such non-photic entrainment on tumor growth rate. Two experiments involved a total of 61 male B6D2F(1) mice synchronized with an alternation of 12 h of light (L) and 12 h of darkness (D) (LD12:12). Mice were randomly allocated to have access to food ad libitum, or restricted to 4 or 6 h during L or D. Rest-activity and body temperature, two circadian outputs, were monitored with an intra-peritoneal sensor. Glasgow osteosarcoma was inoculated into both flanks of each mouse ten days after meal timing onset. Before tumor inoculation, meal timing during D amplified the 24-h rhythms in rest-activity and body temperature with minimal phase alteration as compared to ad libitum feeding. Conversely, meal timing during L induced dominant 12-h or 8-h rhythmic components in activity, nearly doubled the 24-h amplitude of body temperature and shifted its acrophase (time of maximum) from approximately mid-D to approximately mid-L. Thirteen days after tumor inoculation, mean tumor weight (+/- SEM, mg) was 1503 +/- 150 in ad libitum mice, 1077 +/- 157 in mice fed during D and 577 +/- 139 in mice fed during L (ANOVA, p < 0.0001). Overall survival was prolonged in the mice fed during L (median, 17.5 days, d) as compared with those fed during D (14.5 d) or ad libitum (14 d) (Log Rank, p = 0.0035). The internal desynchronization produced by meal timing during L slowed down tumor progression, an effect possibly resulting from improved host-mediated tumor control and/or altered tumor circadian clocks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature / physiology
  • Bone Neoplasms / pathology*
  • Circadian Rhythm
  • Disease Progression
  • Feeding Behavior*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Motor Activity / physiology
  • Neoplasm Transplantation
  • Osteosarcoma / pathology*
  • Survival Rate