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Physical Activity Engagement Worsens Health Outcomes and Limits Exercise Capacity in Growth-restricted Mice
David P Ferguson1, Eric C Leszczynski1, Ashley C McPeek1
1Department of Kinesiology, Michigan State University, East Lansing, MI.
Insights
Growth restriction in mice impaired responses to physical activity, leading to negative cardiac outcomes. Exercise did not improve capacity in growth-restricted animals, contrary to expectations.
Area of Science:
- Cardiovascular Physiology
- Exercise Physiology
- Developmental Biology
Background:
- 161 million children annually experience growth restriction, increasing chronic disease risk.
- Physical activity (PA) is crucial for reducing chronic disease mortality.
- Understanding PA effects on growth-restricted individuals is vital.
Purpose of the Study:
- To investigate the impact of a physical activity intervention (wheel running) on cardiac and skeletal muscle function.
- To compare outcomes in growth-restricted mice (gestational and postnatal) versus controls.
Main Methods:
- A mouse model was used to induce gestational (GUN) and postnatal (PUN) growth restriction.
- Mice underwent a 3-week wheel running intervention followed by maximal exercise testing.
- Cardiac function was assessed via echocardiography, and skeletal muscle adaptations were analyzed through histology.
Main Results:
- Control mice showed a 45% improvement in exercise capacity post-intervention.
- Growth-restricted mice (GUN and PUN) did not improve exercise capacity.
- Negative cardiac outcomes, including reduced ventricular volume and indicators of fibrosis, were observed in PUN mice.
- Skeletal muscle adaptations were mixed, with shifts towards oxidative or glycolytic profiles depending on the muscle group and sex.
Conclusions:
- Growth restriction significantly hinders the beneficial adaptations to physical activity.
- The intervention led to adverse cardiac remodeling in growth-restricted mice.
- Physical activity interventions may have detrimental effects on cardiovascular health in growth-restricted populations.
Introduction:
A total of 161 million children a year are growth restricted, leading to a 47% increased risk of chronic disease in adulthood. Physical activity (PA) reduces the risk of mortality from chronic disease. The purpose of the present investigation was to determine the effect of a PA intervention (wheel running) on cardiac and skeletal muscle capacities in gestational (GUN) and postnatal (PUN) growth-restricted mice as compared with nonrestricted controls (CON).
Methods:
A low-protein cross-fostering FVB mouse model was used to induce growth restriction during gestation and the first 21 d of postnatal life. Mouse pups were recovered on a healthy diet until mature and provided wheel access for 3 wk. At completion of the PA intervention, mice underwent maximal exercise testing on a treadmill, echocardiography, and skeletal muscle histology.
Results:
After the PA intervention, CON mice had a 45% improvement in maximal exercise capacity (P = 0.0390) because of cardiac and skeletal muscle adaptations, but GUN and PUN mice did not. Alarmingly, PUN female mice exposed to wheels had 11.45% lower left ventricular volume (P = 0.0540) and 18% lower left ventricle area (P = 0.0585), with blood flow velocities indicative of cardiac fibrosis (GUN had elevated isovolumetric contraction time P = 0.0374; GUN females and PUN males had longer isovolumetric relaxation time P = 0.0703). PUN male mice had mixed skeletal muscle responses with an oxidative shift in the diaphragm (P = 0.0162) but a glycolytic shift in the extensor digitorum longus (P = 0.0647). PUN female mice had a glycolytic shift in the soleus after wheel running.
Conclusions:
Unexpectedly, growth-restricted mice were nonresponders to a PA intervention and displayed negative cardiac outcomes.
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