title: Long-term exercise training prevents mammary tumorigenesis-induced muscle wasting in rats through the regulation of TWEAK signalling.
abstract: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting.
  
  
  
  Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Fifteen animals from each group were exposed to N-Methyl-N-nitrosourea carcinogen. Animals in exercise groups were submitted to moderate treadmill exercise for 35 weeks. After the experimental period, animals were killed and gastrocnemius muscles were harvested for morphological and biochemical analysis.
  
  
  
  We verified that exercise training prevented tumour-induced TWEAK/NF-κB signalling in skeletal muscle with a beneficial impact in fibre cross-sectional area and metabolism. Indeed, 35 weeks of exercise training promoted the upregulation of PGC-1α and oxidative phosphorylation complexes. This exercise-induced muscle remodelling in tumour-bearing animals was associated with less malignant mammary lesions.
  
  
  
  Data support the benefits of an active lifestyle for the prevention of muscle wasting secondary to breast cancer, highlighting TWEAK/NF- κB signalling as a potential therapeutic target for the preservation of muscle mass.
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.|CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: A I
authors.initials: AI
authors.lastname: Padrão
authors.affiliation: CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: A C C
authors.initials: AC
authors.lastname: Figueira
authors.affiliation: CITAB, Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: A I
authors.initials: AI
authors.lastname: Faustino-Rocha
authors.affiliation: CITAB, Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Gama
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: M M
authors.initials: MM
authors.lastname: Loureiro
authors.affiliation: CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: M J
authors.initials: MJ
authors.lastname: Neuparth
authors.affiliation: CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.|Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Moreira-Gonçalves
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.|Department of Medical Sciences and Institute for Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Vitorino
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Amado
authors.affiliation: Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: L L
authors.initials: LL
authors.lastname: Santos
authors.affiliation: CITAB, Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: P A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: J A
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D000074049:Cytokine TWEAK; D004195:Disease Models, Animal; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000150:complications*; D008565:Membrane Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000096:biosynthesis*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000074049:Cytokine TWEAK; D008565:Membrane Proteins; D016328:NF-kappa B; C497771:Tnfsf12 protein, rat; D048069:Tumor Necrosis Factors
keywords: NF-κB signalling; gastrocnemius; inflammation; mammary carcinogenesis; oxidative metabolism