Effects of food restriction on voluntary wheel-running behavior and body mass in selectively bred High Runner lines of mice

•Female mice from 4 selectively bred High Runner (HR) lines were food-restricted.•20 % food restriction did not significantly affect daily wheel-running distance.•40 % food restriction significantly reduced running distance only in HR mice (−11.4 %).•Only 40 % food restriction significantly reduced body mass: HR −2.6 % and c - 2.0 %.•Results call for studies of compensatory mechanisms that allow this insensitivity. Food restriction can have profound effects on various aspects of behavior, physiology, and morphology. Such effects might be amplified in animals that are highly active, given that physical activity can represent a substantial fraction of the total daily energy budget. More specifically, some effects of food restriction could be associated with intrinsic, genetically based differences in the propensity or ability to perform physical activity. To address this possibility, we studied the effects of food restriction in four replicate lines of High Runner (HR) mice that have been selectively bred for high levels of voluntary wheel running. We hypothesized that HR mice would respond differently than mice from four non-selected Control (C) lines. Healthy adult females from generation 65 were housed individually with wheels and provided access to food and water ad libitum for experimental days 1–19 (Phase 1), which allowed mice to attain a plateau in daily running distances. Ad libitum food intake of each mouse was measured on days 20–22 (Phase 2). After this, each mouse experienced a 20 % food restriction for 7 days (days 24–30; Phase 3), and then a 40 % food restriction for 7 additional days (days 31–37; Phase 4). Mice were weighed on experimental days 1, 8, 9, 15, 20, and 23–37 and wheel-running activity was recorded continuously, in 1-minute bins, during the entire experiment. Repeated-measures ANOVA of daily wheel-running distance during Phases 2–4 indicated that HR mice always ran much more than C, with values being 3.29-fold higher during the ad libitum feeding trial, 3.58-fold higher with -20 % food, and 3.06-fold higher with -40 % food. Seven days of food restriction at -20 % did not significantly reduce wheel-running distance of either HR (-5.8 %, P = 0.0773) or C mice (-13.3 %, P = 0.2122). With 40 % restriction, HR mice showed a further decrease in daily wheel-running distance (P = 0.0797 vs. values at 20 % restriction), whereas C mice did not (P = 0.4068 vs. values at 20 % restriction) and recovered to levels similar to those on ad libitum