Effects of Wheel Running on Health-Related Outcomes in Growth Restricted Mice.

Abstract

Growth restriction caused by early life undernutrition leads to an increased risk of cardiovascular disease, hypertension, type II diabetes and sarcopenia. However, limited information exists on the beneficial effects of physical activity engagement in growth restricted individuals. PURPOSE: To determine the effects of wheel running access on health-related outcomes in growth restricted mice. METHODS: Mice were undernourished in gestation (GUN, N=15) or lactation (PUN, N=17) by feeding FVB mothers a low protein diet (8% protein). The control group (CON, N=14) was fed a normal protein diet (20% protein) throughout gestation and lactation. At postnatal day 21 (PN21), all pups were weaned and refed with the control diet. At PN45, mice were singly housed and either given access to a free moving running wheel (VOL-wheel access) or used as a non-active control (SED-sedentary). At PN70 a maximal treadmill test was performed to determine exercise capacity, and at PN72 echocardiography was performed to evaluate cardiovascular function. RESULTS: Final body weight showed SED PUN (M: 21.22±2.07 g, F: 17.42±1.7 g) weighed significantly (P=0.0002) less than SED CON (M: 26.83±2.2 g, F: 20.65±1.65 g) and SED GUN (M: 26.9±1.5 g, F: 19.98±1.6 g) mice, while the VOL CON mice (M: 24.9±1.62 g, F: 23.0±1.42 g) were significantly larger (P=0.0441) than VOL PUN mice (M: 22.6±2.7 g, F: 20.0±2.26 g). Wheel access improved treadmill running time to exhaustion in CON (P=0.045, VOL: 1078±47s, SED: 936±40s), and GUN mice (P=0.042; VOL 1021±39s SED 890±44s), but not PUN mice (P=0.59; VOL 933±31s and SED 908±32s). Echoes showed heart rate was significantly lowered (P=0.002) in GUN mice (VOL:366±11 bpm; SED: 421±10 bpm) with running wheel access. Stroke volume was also significantly higher (P=0.02) in GUN mice (VOL: 27±1.2 uL; SED: 23±1.1 uL). VOL CON (1.64±0.08mm) mice had a significantly greater (P=0.05) left ventricular anterior wall thickness at systole than SED CON (1.38±0.08mm). CONCLUSION: Voluntary wheel access does not attenuate growth-restriction in PUN mice nor does it improve maximal treadmill tests. This is due to a lack of improvements in cardiac function for PUN mice, despite access to voluntary wheel running, while GUN mice did improve.