Summary Mammals expend energy in many ways, including basic cellular maintenance and repair, digestion, thermoregulation, locomotion, growth and reproduction. These processes can vary tremendously among species and individuals, potentially leading to large variation in daily energy expenditure (DEE). Locomotor energy costs can be substantial for large-bodied species and those with high-activity lifestyles. For humans in industrialized societies, locomotion necessary for daily activities is often relatively low, so it has been presumed that activity energy expenditure and DEE are lower than in our ancestors. Whether this is true and has contributed to a rise in obesity is controversial. In humans, much attention has centered on spontaneous physical activity (SPA) or non-exercise activity thermogenesis (NEAT), the latter sometimes defined so broadly as to include all energy expended due to activity, exclusive of volitional exercise. Given that most people in Western societies engage in little voluntary exercise, increasing NEAT may be an effective way to maintain DEE and combat overweight and obesity. One way to promote NEAT is to decrease the amount of time spent on sedentary behaviours (e.g. watching television). The effects of voluntary exercise on other components of physical activity are highly variable in humans, partly as a function of age, and have rarely been studied in rodents. However, most rodent studies indicate that food consumption increases in the presence of wheels; therefore, other aspects of physical activity are not reduced enough to compensate for the energetic cost of wheel running. Most rodent studies also show negative effects of wheel access on body fat, especially in males. Sedentary behaviours per se have not been studied in rodents in relation to obesity. Several lines of evidence demonstrate the important role of dopamine, in addition to other neural signaling networks (e.g. the endocannabinoid system), in the control of voluntary exercise. A largely separate literature points to a key role for orexins in SPA and NEAT. Brain reward centers are involved in both types of physical activities and eating behaviours, likely leading to complex interactions. Moreover, voluntary exercise and, possibly, eating can be addictive. A growing body of research considers the relationships between personality traits and physical activity, appetite, obesity and other aspects of physical and mental health. Future studies should explore the neurobiology, endocrinology and genetics of physical activity and sedentary behaviour by examining key brain areas, neurotransmitters and hormones involved in motivation, reward and/or the regulation of energy balance.

We evaluated the effect of voluntary exercise on spontaneous physical activity (SPA) and food consumption in mice from 4 replicate lines bred for 57 generations for high voluntary wheel running (HR) and from 4 non-selected control (C) lines. Beginning at ~24 days of age, mice were housed in standard cages or in cages with attached wheels. Wheel activity and SPA were monitored in 1-min intervals. Data from the 8th week of the experiment were analyzed because mice were sexually mature and had plateaued in body mass, weekly wheel running distance, SPA, and food consumption. Body mass, length, and masses of the retroperitoneal fat pad, liver, and heart were recorded after the 13th week. SPA of both HR and C mice decreased with wheel access, due to reductions in both duration and average intensity of SPA. However, total activity duration (SPA+wheel running; min/day) was ~1/3 greater when mice were housed with wheels, and food consumption was significantly increased. Overall, food consumption in both HR and C mice was more strongly affected by wheel running than by SPA. Duration of wheel running had a stronger effect than average speed, but the opposite was true for SPA. With body mass as a covariate, chronic wheel access significantly reduced fat pad mass and increased heart mass in both HR and C mice. Given that both HR and C mice housed with wheels had increased food consumption, the energetic cost of wheel running was not fully compensated by concomitant reductions in SPA. The experiment demonstrates that both duration and intensity of both wheel running and SPA were significant predictors of food consumption. This sort of detailed analysis of the effects of different aspects of physical activity on food consumption has not previously been reported for a non-human animal, and it sets the stage for longitudinal examination of energy balance and its components in rodent models.

Our results fail to provide support for the systemic robusticity hypothesis, suggesting it is important to rethink the long-standing theory that increased CVT in Homo erectus reflects increased physical activity compared other hominin species.

Force magnitudes have been suggested to drive the structural response of bone to exercise. As importantly, the degree to which any given bone can adapt to functional challenges may be enabled, or constrained, by regional variation in the capacity of marrow progenitors to differentiate into bone-forming cells. Here, we investigate the relationship between bone adaptation and mesenchymal stem cell (MSC) responsivity in growing mice subject to exercise. First, using a force plate, we show that peak external forces generated by forelimbs during quadrupedal locomotion are significantly higher than hindlimb forces. Second, by subjecting mice to treadmill running and then measuring bone structure with μCT, we show that skeletal effects of exercise are site-specific but not defined by load magnitudes. Specifically, in the forelimb, where external forces generated by running were highest, exercise failed to augment diaphyseal structure in either the humerus or radius, nor did it affect humeral trabecular structure. In contrast, in the ulna, femur and tibia, exercise led to significant enhancements of diaphyseal bone areas and moments of area. Trabecular structure was also enhanced by running in the femur and tibia. Finally, using flow cytometry, we show that marrow-derived MSCs in the femur are more responsive to exercise-induced loads than humeral cells, such that running significantly lowered MSC populations only in the femur. Together, these data suggest that the ability of the progenitor population to differentiate toward osteoblastogenesis may correlate better with bone structural adaptation than peak external forces caused by exercise.

Skeletal muscles attach to bone at their origins and insertions, and the interface where tendon meets bone is termed the attachment site or enthesis. Mechanical stresses at the muscle/tendon‐bone interface are proportional to the surface area of the bony attachment sites, such that a larger attachment site will distribute loads over a wider area. Muscles that are frequently active and/or are of larger size should cause attachment sites to hypertrophy (training effect); however, experimental studies of animals subjected to exercise have provided mixed results. To enhance our ability to detect training effects (a type of phenotypic plasticity), we studied a mouse model in which 4 replicate lines of High Runner (HR) mice have been selectively bred for 57 generations. Selection is based on the average number of wheel revolutions on days 5 & 6 of a 6‐day period of wheel access as young adults (6–8 weeks old). Four additional lines are bred without regard to running and serve as non‐selected controls (C). On average, mice from HR lines voluntarily run ~3 times more than C mice on a daily basis. For this study, we housed 50 females (half HR, half C) with wheels (Active group) and 50 (half HR, half C) without wheels (Sedentary group) for 12 weeks starting at weaning (~3 weeks old). We tested for evolved differences in muscle attachment site surface area between HR and C mice, plastic changes resulting from chronic exercise, and their interaction. We used a precise, highly repeatable method for quantifying the three‐dimensional (3D) surface area of four muscle attachment sites: the humerus deltoid tuberosity (the insertion point for the spinodeltoideus, superficial pectoralis, and acromiodeltoideus), the femoral third trochanter (the insertion point for the quadratus femoris), the femoral lesser trochanter (the insertion point for the iliacus muscle), and the femoral greater trochanter (insertion point for the middle gluteal muscles). In univariate analyses, with body mass as a covariate, mice in the Active group had significantly larger humerus deltoid tuberosities than Sedentary mice, with no significant difference between HR and C mice and no interaction between exercise treatment and linetype. These differences between Active and Sedentary mice were also apparent in the multivariate analyses. Surface areas of the femoral third trochanter, femoral lesser trochanter, and femoral greater trochanter were unaffected by either chronic wheel access or selective breeding. Our results, which used robust measurement protocols and relatively large sample sizes, demonstrate that muscle attachment site morphology can be (but is not always) affected by chronic exercise experienced during ontogeny. However, contrary to previous results for other aspects of long bone morphology, we did not find evidence for evolutionary coadaptation of muscle attachments with voluntary exercise behavior in the HR mice.