Eccentric contraction-induced myofiber growth in tumor-bearing mice.
Cancer cachexia is characterized by the progressive loss of skeletal muscle mass. While mouse skeletal muscle's response to an acute bout of stimulated low-frequency concentric muscle contractions is disrupted by cachexia, gaps remain in our understanding of cachexia's effects on eccentric contraction-induced muscle growth. The purpose of this study was to determine whether repeated bouts of stimulated high-frequency eccentric muscle contractions [high-frequency electrical muscle stimulation (HFES)] could stimulate myofiber growth during cancer cachexia progression, and whether this training disrupted muscle signaling associated with wasting. Male Apc(Min/+) mice initiating cachexia (N = 9) performed seven bouts of HFES-induced eccentric contractions of the left tibialis anterior muscle over 2 wk. The right tibialis anterior served as the control, and mice were killed 48 h after the last stimulation. Age-matched C57BL/6 mice (N = 9) served as wild-type controls. Apc(Min/+) mice lost body weight, muscle mass, and type IIA, IIX, and IIB myofiber cross-sectional area. HFES increased myofiber cross-sectional area of all fiber types, regardless of cachexia. Cachexia increased muscle noncontractile tissue, which was attenuated by HFES. Cachexia decreased the percentage of high succinate dehydrogenase activity myofibers, which was increased by HFES, regardless of cachexia. While cachexia activated AMP kinase, STAT3, and ERK1/2 signaling, HFES decreased AMP kinase phosphorylation, independent of the suppression of STAT3. These results demonstrate that cachectic skeletal muscle can initiate a growth response to repeated eccentric muscle contractions, despite the presence of a systemic cachectic environment.
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Justin P
JP
Hardee
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Joshua E
JE
Mangum
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Song
S
Gao
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Shuichi
S
Sato
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Kimbell L
KL
Hetzler
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Melissa J
MJ
Puppa
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and.
Dennis K
DK
Fix
Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, South Carolina; and Center for Colon Cancer Research, University of South Carolina, Columbia, South Carolina carsonj@mailbox.sc.edu.
James A
JA
Carson
D019412:Anatomy, Cross-Sectional; D000818:Animals; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000235:genetics; D001835:Body Weight; D002100:Cachexia / Q000473:pathology / Q000503:physiopathology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D004558:Electric Stimulation; D007249:Inflammation / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size; D010805:Physical Conditioning, Animal; D015398:Signal Transduction; D013385:Succinate Dehydrogenase / Q000378:metabolism
C577336:Anapc1 protein, mouse; D064189:Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome; D013385:Succinate Dehydrogenase
cancer cachexia; eccentric contractions; high-frequency electrical stimulation; muscle inflammation; myofiber growth