Cell Metabolism
Volume 33, Issue 5, 4 May 2021, Pages 957-970.e6
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Article
Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers

https://doi.org/10.1016/j.cmet.2021.02.017Get rights and content
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Highlights

  • Here, we investigate the dose-response effects of exercise training in healthy subjects

  • Excessive exercise training induces substantial mitochondrial respiratory impairment

  • Mitochondrial impairment is associated with impaired glucose tolerance

  • Despite excessive training, markers of global oxidative stress were unchanged

Summary

Exercise training positively affects metabolic health through increased mitochondrial oxidative capacity and improved glucose regulation and is the first line of treatment in several metabolic diseases. However, the upper limit of the amount of exercise associated with beneficial therapeutic effects has not been clearly identified. Here, we used a training model with a progressively increasing exercise load during an intervention over 4 weeks. We closely followed changes in glucose tolerance, mitochondrial function and dynamics, physical exercise capacity, and whole-body metabolism. Following the week with the highest exercise load, we found a striking reduction in intrinsic mitochondrial function that coincided with a disturbance in glucose tolerance and insulin secretion. We also assessed continuous blood glucose profiles in world-class endurance athletes and found that they had impaired glucose control compared with a matched control group.

Keywords

exercise
mitochondria
mitochondrial dysfunction
high-intensity interval training
insulin resistance
metabolic dysfunction
glucose tolerance
mitochondrial dynamics
exercise adaptations
continuous glucose monitoring
athletes

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