Effects of meal timing on tumor progression in mice.
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.
Wu
M W
MW
INSERM E 0354 Chronothérapeutique des cancers, Hôpital Paul Brousse and Université Paris XI, 94807 Villejuif Cedex, France.
Li
X M
XM
Xian
L J
LJ
Lévi
F
F
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001859:Bone Neoplasms / Q000473:pathology*; D002940:Circadian Rhythm; D018450:Disease Progression; D005247:Feeding Behavior; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000502:physiology; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000473:pathology*; D015996:Survival Rate