title: Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia.
abstract: OBJECTIVE
  The appropriate mode of exercise training for cancer cachexia is not well-established. Using the colon-26 (C26) mouse model of cancer cachexia, we defined and compared the skeletal muscle responses to aerobic and resistance training.
  
  
  METHODS
  Twelve-month old Balb/c mice were initially assigned to control, aerobic training (AT; wheel running), or resistance training (RT; ladder climbing) (n=16-17/group). After 8weeks of training, half of each group was injected with C26 tumor cells, followed by 3 additional weeks of training. Body composition and neuromuscular function was evaluated pre- and post-training. Muscles were collected post-training and analyzed for fiber cross-sectional area (CSA), Akt-mTOR signaling, and expression of insulin-like growth factor-I (IGF-I) and myogenic regulatory factors.
  
  
  RESULTS
  Total body mass decreased (p<0.05) in C26 (-8%), AT+C26 (-18%), and RT+C26 (-15%) but not control. Sensorimotor function declined (p<0.05) in control (-16%), C26 (-13%), and RT+C26 (-23%) but not AT+C26. Similarly, strength/body weight decreased (p<0.05) in control (-7%), C26 (-21%), and RT+C26 (-10%) but not AT+C26. Gastrocnemius mass/body weight tended to be greater in AT+C26 vs. C26 (+6%, p=0.09). Enlargement of the spleen was partially corrected in AT+C26 (-27% vs. C26, p<0.05). Fiber CSA was lower in all C26 groups vs. control (-32% to 46%, p<0.05); however, the effect size calculated from C26 and AT+C26 was large (+24%, d=1.04). Phosphorylated levels of mTOR in AT+C26 exceeded C26 (+32%, p<0.05). RT+C26 showed greater mRNA expression (p<0.05) of IGF-IEa (+79%) and myogenin (+126%) with a strong tendency for greater IGF-IEb (+127%, p=0.069) vs.
  
  
  CONCLUSIONS
  Aerobic or resistance training was unable to prevent tumor-induced body weight loss. However, aerobic training may have preserved function, reduced the inflammatory response of the spleen, and marginally rescued muscle mass possibly through activation of mTOR. Aerobic training may therefore have therapeutic value for patients with cancer cachexia. In contrast, resistance training induced the expression of genes associated with muscle damage and repair. This gene response may be supportive of excessive stress generated by high resistance loading in a tumor-bearing state.
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA; The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA.
authors.forename: Andy V
authors.initials: AV
authors.lastname: Khamoui
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA.
authors.forename: Bong-Sup
authors.initials: BS
authors.lastname: Park
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA; The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA.
authors.forename: Do-Houn
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA; The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA.
authors.forename: Ming-Chia
authors.initials: MC
authors.lastname: Yeh
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA.
authors.forename: Seung-Lyul
authors.initials: SL
authors.lastname: Oh
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA; The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA.
authors.forename: Marcus L
authors.initials: ML
authors.lastname: Elam
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA; The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA; Department of Kinesiology and Health Promotion, California State Polytechnic University, Pomona, CA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Jo
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA; The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA.
authors.forename: Bahram H
authors.initials: BH
authors.lastname: Arjmandi
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Salazar
authors.affiliation: The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA; Department of Chemical and Biomedical Engineering and The National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, USA.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Grant
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Contreras
authors.affiliation: Department of Exercise Science, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA; The Center for Advancing Exercise and Nutrition Research on Aging, Florida State University, Tallahassee, FL, USA. Electronic address: jkim6@fsu.edu.
authors.forename: Jeong-Su
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008807:Mice, Inbred BALB C; D009043:Motor Activity; D024510:Muscle Development; D018908:Muscle Weakness / Q000209:etiology / Q000517:prevention & control; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D055070:Resistance Training; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C546843:mTOR protein, mouse; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Cachectic; Exercise training; Ladder climbing; Muscle atrophy; Myogenin