title: Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice.
abstract: Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P < 0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P < 0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P < 0.001), maintained lean body mass (P < 0.001) and muscle strength (P < 0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Hojman
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonas
authors.initials: J
authors.lastname: Fjelbye
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Bo
authors.initials: B
authors.lastname: Zerahn
authors.affiliation: Copenhagen University Hospital, The University Hospitals Centre for Health Care Research (UCSF), Copenhagen, Denmark.
authors.forename: Jesper F
authors.initials: JF
authors.lastname: Christensen
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christine
authors.initials: C
authors.lastname: Dethlefsen
authors.affiliation: Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Camilla K
authors.initials: CK
authors.lastname: Lonkvist
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Brandt
authors.affiliation: Institute of Biomedicine, University of Aarhus, Aarhus C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Gissel
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
authors.affiliation: Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark.
authors.forename: Julie
authors.initials: J
authors.lastname: Gehl
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D018149:Glucose Intolerance / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D006003:Glycogen / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D009133:Muscular Atrophy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012420:Running / Q000502:physiology; D015398:Signal Transduction
chemical_list: D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin