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Treadmill running of ∼0.9 km/day has had inconsistent effects on spontaneous intestinal polyp development in C57BL/6J-ApcMin/J (Min) mice; the amount of energy expenditure and/or a lack of hormonal changes could account for this variability. The purpose of this study was to examine the effects of a negative energy balance induced by voluntary wheel running on polyps, insulin-like growth factor-1 (IGF-1) and corticosterone inMinmice. Seven-week-old maleMinmice were randomly assigned to control (CON,n= 23) or wheel running (EX,n= 24) conditions for a 10-week study period. All mice had water and AIN-76A dietad libitumfor the first ∼3 weeks on study, after which the EX group was pair-fed to the CON group to maintain a negative energy balance due to the exercise. EX mice voluntarily ran 3.8 km/day (2.7–6.0 km/day) (median, interquartile range) and weighed less than CON mice throughout the study. More CON mice died before the end of the study versus EX mice (26 versus 0%,P&lt; 0.01). CON mice had significantly more polyps versus EX mice (21.6 ± 1.5 versus 16.9 ± 2.0,P&lt; 0.01; mean ± SE), and daily running distance in EX was inversely correlated with total polyp number (r= −0.70,P&lt; 0.01). Urinary corticosterone output (P&lt; 0.01) and serum IGF-1 were significantly higher in EX than CON (P&lt; 0.001); however, total polyp number was unrelated to corticosterone (r= 0.05,P= 0.84) and IGF-1 (r= −0.01,P= 0.93). In this study, a negative energy balance produced by wheel running exercise and restricted feeding decreased polyp burden in maleMinmice and appeared to have a dose–response effect on polyp number. Although EX affected IGF-1 and corticosterone, neither marker was related to total polyp number.

Negative energy balance induced by voluntary wheel running inhibits polyp development in APC Min mice