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High-Frequency Stimulation on Skeletal Muscle Maintenance in Female Cachectic Mice

SATO, SHUICHI1,2; GAO, SONG1; PUPPA, MELISSA J.1; KOSTEK, MATTHEW C.1; WILSON, L. BRITT3; CARSON, JAMES A.1

Medicine & Science in Sports & Exercise: September 2019 - Volume 51 - Issue 9 - p 1828–1837
doi: 10.1249/MSS.0000000000001991
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Cancer cachexia, an unintentional body weight loss due to cancer, affects patients’ survival, quality of life, and response to chemotherapy. Although exercise training is a promising intervention to prevent and treat cancer cachexia, our mechanistic understanding of cachexia’s effect on contraction-induced muscle adaptation has been limited to the examination of male mice. Because sex can affect muscle regeneration and response to contraction in humans and mice, the effect of cachexia on the female response to eccentric contraction warrants further investigation.

Purpose The purpose of this study was to determine whether high-frequency electric stimulation (HFES) could attenuate muscle mass loss during the progression of cancer cachexia in female tumor-bearing mice.

Methods Female wild-type (WT) and ApcMin/+ (Min) mice (16–18 wk old) performed either repeated bouts or a single bout of HFES (10 sets of 6 repetitions, ~22 min), which eccentrically contracts the tibialis anterior (TA) muscle. TA myofiber size, oxidative capacity, anabolic signaling, and catabolic signaling were examined.

Results Min had reduced TA muscle mass and type IIa and type IIb fiber sizes compared with WT. HFES increased the muscle weight and the mean cross-sectional area of type IIa and type IIb fibers in WT and Min mice. HFES increased mTOR signaling and myofibrillar protein synthesis and attenuated cachexia-induced AMPK activity. HFES attenuated the cachexia-associated decrease in skeletal muscle oxidative capacity.

Conclusion HFES in female mice can activate muscle protein synthesis through mTOR signaling and repeated bouts of contraction can attenuate cancer-induced muscle mass loss.

1Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC

2School of Kinesiology, University of Louisiana at Lafayette, Lafayette, LA

3Department of Pharmacology, Physiology, and Neuroscience, School of Medicine, University of South Carolina, Columbia, SC

Address for correspondence: Shuichi Sato, Ph.D., School of Kinesiology, University of Louisiana at Lafayette, 225 Cajundome Blvd, Lafayette, LA 70506; E-mail: shuichi.sato@louisiana.edu.

Submitted for publication January 2019.

Accepted for publication March 2019.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.acsm-msse.org).

Online date: April 1, 2019

© 2019 American College of Sports Medicine