Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 214, Issue -, Pages 137-147Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2016.03.071
Keywords
Heart failure; Skeletal muscle; IGF-I/Akt/mTOR; Aerobic exercise training; Atrophy
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil (FAPESP) [2003/10442-9]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-PDEE) [2010/4302-10-9]
- FAPESP [2010/50048-1, 2014/25957-9, 2012/22817-6]
- Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) [302201/2011-4, 304205/2011-7]
- Telethon
- ASI
- PRIN
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [10/50048-1] Funding Source: FAPESP
Ask authors/readers for more resources
Background: Exercise intolerance is one of the main clinical symptoms of heart failure (HF) and is associated with skeletal muscle wasting due to an imbalance between proteolysis and protein synthesis. In this study, we tested whether aerobic exercise training (AET) would counteract skeletal muscle atrophy by activating IGF-I/Akt/mTOR pathway in HF mice. Methods: Sympathetic hyperactivity induced HF mice were assigned into 8-week moderate intensity AET. Untrained wild type and HF mice were used as control. Soleus cross sectional area was evaluated by histochemistry and motor performance by rotarod. 26S proteasome activity was assessed by fluorimetric assay, and components of IGF-I/Akt/mTOR pathway or myostatin pathway by qRT-PCR or immunoblotting. A different subset of mice was used to evaluate the relative contribution of mTOR inhibition (rapamycin) or activation (leucine) on AET-induced changes in muscle mass regulation. Results: AET prevented exercise intolerance and impaired motor performance in HF mice. These effects were associated with attenuation of soleus atrophy. Rapamycin treatment precluded AET effects on soleus mass in HF mice suggesting the involvement of IGF signaling pathway in this response. In fact, AET increased IGF-I Ea and IGF-I Pan mRNA levels, while it reduced myostatin and Smad2 mRNA levels in HF mice. At protein levels, AET prevented reduced expression levels of IGF-I, pAkt (at basal state), as well as, p4E-BP1 and pP70(S6K) (leucine-stimulated state) in HF mice. Additionally, AET prevented 26S proteasome hyperactivity in HF mice. Conclusions: Taken together, our data provide evidence for AET-induced activation of IGF-I/Akt/mTOR signaling pathway counteracting HF-induced muscle wasting. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available