Exercise training impacts skeletal muscle remodelling induced by metabolic syndrome in ZSF1 rats through metabolism regulation

abstract

Metabolic syndrome (MetS), characterized by a set of conditions that include obesity, hypertension, and dyslipidemia, is associated with increased cardiovascular risk. Exercise training (EX) has been reported to improve MetS management, although the underlying metabolic adaptations that drive its benefits remain poorly understood. This work aims to characterize the molecular changes induced by EX in skeletal muscle in MetS, focusing on gastrocnemius metabolic remodelling. 1H NMR metabolomics and molecular assays were employed to assess the metabolic profile of skeletal muscle tissue from lean male ZSF1 rats (CTL), obese sedentary male ZSF1 rats (MetS-SED), and obese male ZF1 rats submitted to 4 weeks of treadmill EX (5 days/week, 60 min/day, 15 m/ min) (MetS-EX). EX did not counteract the significant increase of body weight and circulating lipid profile, but had an anti-inflammatory effect and improved exercise capacity. The decreased gastrocnemius mass observed in MetS was paralleled with glycogen degradation into small glucose oligosaccharides, with the release of glucose 1-phosphate, and an increase in glucose-6-phosphate and glucose levels. Moreover, sedentary MetS animals' muscle exhibited lower AMPK expression levels and higher amino acids' metabolism such as glutamine and glutamate, compared to lean animals. In contrast, the EX group showed changes suggesting an increase in fatty acid oxidation and oxidative phosphorylation. Additionally, EX mitigated MetS-induced fiber atrophy and fibrosis in the gastrocnemius muscle. EX had a positive effect on gastrocnemius metabolism by enhancing oxidative metabolism and, consequently, reducing susceptibility to fatigue. These findings reinforce the importance of prescribing EX programs to patients with MetS.

keywords

PRESERVED EJECTION FRACTION; HEART-FAILURE; FUNCTIONAL ALTERATIONS; GLUTAMINE-METABOLISM; INSULIN SENSITIVITY; PHYSICAL-ACTIVITY; WEIGHT-LOSS; AMINO-ACID; MITOCHONDRIAL; OBESITY

subject category

Biochemistry & Molecular Biology; Biophysics; Cell Biology

authors

Nogueira-Ferreira, R; Santos, I; Ferreira, R; Fontoura, D; Sousa-Mendes, C; Falcao-Pires, I; Lourenço, AP; Leite-Moreira, A; Duarte, IF; Moreira-Gonçalves, D

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

Rede Nacional de Ressonância Magnética Nuclear (PTNMR)

acknowledgements

This work was supported by "Fundacao para a Ciencia e a Tecnologia" - FCT, European Union, QREN, FEDER and COMPETE for funding the LAQV-REQUIMTE (UIDB/50006/2020) , UnIC (UIDB/IC/00051/2020 and UIDP/00051/2020) , CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 & amp; LA/P/0006/2020) and CIA-FEL (UIDB/00617/2020) research units, RISE - Health Research Network-From the Lab to the Community (LA/P/0053/2020) , ITR-Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020) , and the research projects DOCnet (NORTE-01-0145-FEDER-000003) and NETDIAMOND (SAICT-PAC/0047/2015) . The NMR spectrometer is part of the National NMR Network (PTNMR) , partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC) . Dulce Fontoura is funded by FCT with Fellowship Grant SFRH/BD/126088/2016. Rita Nogueira-Ferreira acknowledges FCT for the research contract CEECIND/03935/2021 under the CEEC Individual 2021.