Short-term voluntary exercise in the rat causes bone modeling without initiating a physiological stress response

Abstract

research has revealed a neuroendocrine connection between the skeleton and metabolism. Exercise alters both bone modeling and energy balance and may be useful in further developing our understanding of this complex interplay. However, research in this field requires an animal model of exercise that does not cause a physiological stress response in the exercised subjects. In this study, we develop a model of short-term voluntary exercise in the female rat that causes bone modeling without causing stress. Rats were randomly assigned to one of three age-matched groups: control, tower climbing, and squat exercise (rising to an erect bipedal stance). Exercise for 21 days resulted in bone modeling as assessed by peripheral quantitative computed tomography. Fecal corticosterone output was used to assess physiological stress at three time points during the study (preexercise, early exercise, and late in the exercise period). There were no differences in fecal corticosterone levels between groups or time points. This model of voluntary exercise in the rat will be useful for future studies of the influence of exercise on the relationship between skeletal and metabolic health and may be appropriate for investigation of the developmental origins of those effects. computed tomography; corticosterone; exercise; metabolism; stress RECENT ADVANCES IN OUR UNDERSTANDING of the dynamic relationship between body structure and metabolism have revealed a neuroendocrine connection between bone remodeling and energy balance, with both bone and fat acting as endocrine organs (14). The osteoblast-specific protein osteocalcin regulates glucose handling through effects on insulin secretion and sensitivity (33). This action is in turn mediated by the adipokine leptin, which inhibits insulin secretion through direct effects on pancreatic ␤-cells (18) and through inhibition of osteocalcin activity (25). The interplay between bone and metabolism has recently been further elucidated by the discovery that the Forkhead family transcription factor FoxO1, a key regulator of insulin handling in multiple tissues, also acts within the osteoblast to control osteocalcin expression and bioactivity (46).Exercise stimulates modeling of the musculoskeletal system (19, 55, 65), alters metabolism (40), and enhances brain function (17), and thus exercise provides an excellent means of exploring the neuroendocrine connection between bone, fat, and energy balance. The rat model of exercise has been used extensively to study the physiological effects of physical activity using such exercise modalities as swimming (24, 32), running (20,29,41,49,52), jumping (57), tower climbing (43), rising to an erect bipedal stance (11, 64), and weight lifting (62). The effects of exercise on bone have been widely characterized in the rat. Ovariectomized rats undergo changes in bone structure that are nearly identical to those seen in human osteoporosis (28,42), and these animals have proven useful for the study of exercise interventions in osteoporosis treatment (36).In examini...

Voluntary exercise in pregnant rats positively influences fetal growth without initiating a maternal physiological stress response

“…Body length (from the occipital crest to the base of the tail: crown-rump length) was measured twice: once under anesthesia for imaging and again immediately following study termination. Maternal feed efficiency was calculated as the ratio of weight gain to feed intake on a per-cage (2 rats per cage) basis, as described previously (43). The study protocol and all animal procedures were approved by the Massey University Animal Ethics Committee.…”

“…After the habituation period, at 88 -95 days of age, the rats were randomly assigned to one of three age-and weight-matched groups: control, squat exercise, and tower climbing. We previously showed that these exercise models induce bone modeling in nonpregnant rats without initiating a physiological stress response (43).…”

“…pQCT (XCT2000 pQCT scanner, Stratec, Pforzheim, Germany) of the right tibia of each rat was performed as described previously (43). Scans were made 5 mm distal to the tibial plateau (proximal metaphysis) and at 50% of tibial length (middiaphysis) (24), with a voxel size of 0.1 mm and scan speed of 5 mm/s.…”

“…Tower climbing and rising to an erect bipedal stance (squat) are voluntary resistance-type exercises that have been shown to cause bone modeling in rats (37,43,51,52). Both of these exercises require muscle contraction against gravity, although the dynamic and repeated muscular contractions of all four limbs during tower climbing may give it a greater aerobic component than the more isometric bipedal "squat" exercise, which requires the rats to attain a "standing" position on extended hindlimbs and then maintain that position while they eat and drink.…”

“…This is in contrast to the treadmill running and swimming extensively described in pregnant rats (31,35,38,40); these exercises often involve noxious stimuli to the animals and are likely to require greater energy use than squat exercise or tower climbing. Previously, we demonstrated that voluntary tower climbing and squat exercise to obtain food are sufficiently strenuous to cause modeling of the tibia in nonpregnant rats without a concomitant rise in fecal corticosterone levels (43), a measure of stress in the rat. In this study, we used these same exercises in pregnant rats to test the hypothesis that neither tower climbing nor squat exercise would increase maternal fecal corticosterone levels or adversely affect fetal outcomes at day 19 of pregnancy.…”