Hindlimb immobilization induces insulin resistance and elevates mitochondrial ROS production in the hippocampus of female rats

Author:

Kerr Nathan R.1ORCID,Mossman Chandler W.2,Chou Chih-Hsuan1,Bunten Joshua M.1,Kelty Taylor J.134,Childs Thomas E.1,Rector Randy Scott3456ORCID,Arnold William David4789,Grisanti Laurel A.1ORCID,Du Xiangwei12,Booth Frank W.13810ORCID

Affiliation:

1. Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, United States

2. Veterinary Medical Diagnostic Laboratory, University of Missouri, Columbia, Missouri, United States

3. Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States

4. NextGen Precision Health, University of Missouri, Columbia, Missouri, United States

5. Research Service, Harry S. Truman Memorial Veterans Medical Center, University of Missouri, Columbia, Missouri, United States

6. Department of Medicine, University of Missouri, Columbia, Missouri, United States

7. Department of Physical Medicine and Rehabilitation, University of Missouri, Columbia, Missouri, United States

8. Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri, United States

9. Department of Neurology, University of Missouri, Columbia, Missouri, United States

10. Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States

Abstract

Muscle disuse via hindlimb immobilization increased oxidative stress and insulin resistance in the hippocampus. These findings were in association with muscle iron overload in connection with iron dysregulation in the brain. Overall, our work identifies muscle disuse as a contributor to hippocampal dysfunction, potentially through an iron-based muscle-brain axis, highlighting iron dysregulation as a potential novel mechanism in the relationship between muscle health, cognitive function, and Alzheimer’s disease risk.

Funder

Harry S. Truman Memorial Veterans Hospital

Publisher

American Physiological Society

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