Journal article
Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice
Cancers, Vol.11(10), p.1541
10/01/2019
DOI: 10.3390/cancers11101541
PMCID: PMC6826436
PMID: 31614775
Abstract
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 gamma coactivator 1 alpha (PGC1 alpha)-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 PGC1 alpha. 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 PGC1 alpha 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.
Details
- Title: Subtitle
- Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice
- Creators
- Andrea D. Re Cecconi - Mario Negri Institute for Pharmacological ResearchMara Forti - Mario Negri Institute for Pharmacological ResearchMichela Chiappa - Mario Negri Institute for Pharmacological ResearchZhiyong Zhu - University of IowaLeonid Zingman - University of IowaLuigi Cervo - Mario Negri Institute for Pharmacological ResearchLuca Beltrame - Mario Negri Institute for Pharmacological ResearchSergio Marchini - Mario Negri Institute for Pharmacological ResearchRosanna Piccirillo - Mario Negri Institute for Pharmacological Research
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.11(10), p.1541
- DOI
- 10.3390/cancers11101541
- PMID
- 31614775
- PMCID
- PMC6826436
- NLM abbreviation
- Cancers (Basel)
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Publisher
- Mdpi
- Number of pages
- 27
- Grant note
- 11423 / ASSOCIAZIONE ITALIANA RICERCA SUL CANCRO (AIRC Start-UP grant); Fondazione AIRC per la ricerca sul cancro 2014-1164 / FONDAZIONE CARIPLO; Fondazione Cariplo
- Language
- English
- Date published
- 10/01/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984359594902771
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