Recovery from FOLFOX chemotherapy-induced systemic and skeletal muscle metabolic dysfunction in mice

Author:

Halle Jessica L.1ORCID,Counts Brittany R.1,Paez Hector G.2,Baumfalk Dryden R.3,Zhang Quan1,Mohamed Junaith S.4ORCID,Glazer Evan S.5,Puppa Melissa J.6,Smuder Ashley J.3,Alway Stephen E.2ORCID,Carson James A.1

Affiliation:

1. Integrative Muscle Biology Laboratory, Division of Regenerative and Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, United States

2. Laboratory of Muscle Biology and Sarcopenia, Department of Physical Therapy, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, United States

3. Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida, United States

4. Laboratory of Muscle and Nerve, Department of Diagnostic and Health Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, Tennessee, United States

5. Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States

6. College of Health Sciences, The University of Memphis, Memphis, Tennessee, United States

Abstract

The present study demonstrates that FOLFOX chemotherapy induces long-lasting deficits in systemic metabolism. Interestingly, FOLFOX modestly suppressed skeletal muscle AMPK and autophagy signaling in vivo and in vitro. The FOLFOX-induced suppression of muscle metabolic signaling recovered after treatment cessation, independent of systemic metabolic dysfunction. Future research should investigate if activating AMPK during treatment can prevent long-term toxicities to improve health and quality of life of patients with cancer and survivors.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | National Heart, Lung, and Blood Institute

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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