Next Article in Journal
Analysis of A 6-Mirna Signature in Serum from Colorectal Cancer Screening Participants as Non-Invasive Biomarkers for Advanced Adenoma and Colorectal Cancer Detection
Next Article in Special Issue
Plasma Metabolomics Identifies Lipid and Amino Acid Markers of Weight Loss in Patients with Upper Gastrointestinal Cancer
Previous Article in Journal
Tumor Expression of Cyclin-Dependent Kinase 5 (Cdk5) Is a Prognostic Biomarker and Predicts Outcome of Oxaliplatin-Treated Metastatic Colorectal Cancer Patients
Previous Article in Special Issue
The Relationship between Imaging-Based Body Composition Analysis and the Systemic Inflammatory Response in Patients with Cancer: A Systematic Review
Open AccessArticle

Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice

1
Department of Neurosciences, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy
2
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
3
Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
4
Department of Medicine, Medical Center, Department of Veterans Affairs, Iowa City, IA 52246, USA
5
Department of Oncology, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1541; https://doi.org/10.3390/cancers11101541
Received: 7 June 2019 / Revised: 20 September 2019 / Accepted: 9 October 2019 / Published: 12 October 2019
(This article belongs to the Special Issue Cancer Cachexia)
Physical activity improves the prognosis of cancer patients, partly by contrasting the associated muscle wasting (cachexia), through still unknown mechanisms. We asked whether aerobic exercise causes secretion by skeletal muscles of proteins (myokines) that may contrast cachexia. Media conditioned by peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α)-expressing myotubes, reproducing some metabolic adaptations of aerobic exercise, as increased mitochondrial biogenesis and oxidative phosphorylation, restrained constitutively active Forkhead box-containing subfamily O3 (caFoxO3)-induced proteolysis. Microarray analysis identified amphiregulin (AREG), natriuretic peptide precursor B (NppB), musclin and fibroblast growth factor 18 (FGF18) as myokines highly induced by PGC1α. Notably, only musclin tended to be low in muscle of mice with a rare human renal carcinoma; it was reduced in plasma and in muscles of C26-bearing mice and in atrophying myotubes, where PGC1α expression is impaired. Therefore, we electroporated the Tibialis Anterior (TA) of C26-bearing mice with musclin or (its receptor) natriuretic peptide receptor 3 (Npr3)-encoding plasmids and found a preserved fiber area, as a result of restrained proteolysis. Musclin knockout (KO) mice lose more muscle tissue during growth of two distinct cachexia-causing tumors. Running protected C26-bearing mice from cachexia, not changing tumor growth, and rescued the C26-induced downregulation of musclin in muscles and plasma. Musclin expression did not change in overloaded plantaris of mice, recapitulating partially muscle adaptations to anaerobic exercise. Musclin might, therefore, be beneficial to cancer patients who cannot exercise and are at risk of cachexia and may help to explain how aerobic exercise alleviates cancer-induced muscle wasting. View Full-Text
Keywords: muscle wasting; muscle atrophy; aerobic exercise; cancer cachexia; myokine; musclin; PGC1α muscle wasting; muscle atrophy; aerobic exercise; cancer cachexia; myokine; musclin; PGC1α
Show Figures

Graphical abstract

MDPI and ACS Style

Re Cecconi, A.D.; Forti, M.; Chiappa, M.; Zhu, Z.; Zingman, L.V.; Cervo, L.; Beltrame, L.; Marchini, S.; Piccirillo, R. Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice. Cancers 2019, 11, 1541.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop