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

Shuichi Sato, Song Gao, Melissa J. Puppa, Matthew C. Kostek, L. Britt Wilson, James Carson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1828-1837
Number of pages10
JournalMedicine and Science in Sports and Exercise
Volume51
Issue number9
DOIs
StatePublished - Sep 1 2019

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Cachexia
Skeletal Muscle
Electric Stimulation
Maintenance
Muscles
Neoplasms
Muscle Neoplasms
AMP-Activated Protein Kinases
Muscle Proteins
Muscle Contraction
Weight Loss
Regeneration
Body Weight
Quality of Life
Exercise
Weights and Measures
Drug Therapy
Survival

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

High-Frequency Stimulation on Skeletal Muscle Maintenance in Female Cachectic Mice. / Sato, Shuichi; Gao, Song; Puppa, Melissa J.; Kostek, Matthew C.; Wilson, L. Britt; Carson, James.

In: Medicine and Science in Sports and Exercise, Vol. 51, No. 9, 01.09.2019, p. 1828-1837.

Research output: Contribution to journalArticle

Sato, Shuichi ; Gao, Song ; Puppa, Melissa J. ; Kostek, Matthew C. ; Wilson, L. Britt ; Carson, James. / High-Frequency Stimulation on Skeletal Muscle Maintenance in Female Cachectic Mice. In: Medicine and Science in Sports and Exercise. 2019 ; Vol. 51, No. 9. pp. 1828-1837.
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abstract = "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.",
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