Background Resistance to the insulin-sensitising adipocytokine, adiponectin, has been described at the level of the skeletal muscle in patients with chronic heart failure (CHF).
Objective To investigate whether exercise training (ET) would improve skeletal muscle energy metabolism and adiponectin signalling.
Methods In a prospective cohort study, patients with CHF were recruited from the Cardiac Rehabilitation Centre, Antwerp University Hospital. They underwent 4 months' combined endurance–resistance ET. Skeletal muscle mRNA and protein expression of adiponectin, AdipoR1 and downstream metabolic genes were measured.
Results Adiponectin mRNA expression in the nine CHF patients was higher than that in 10 matched healthy subjects (p=0.007), whereas AdipoR1 and downstream-located genes involved in lipid (PPAR-α, ACADM) and glucose metabolism (AMPK, hexokinase2) were down-regulated. Skeletal muscle AdipoR1 correlated with VO2 peak (r=0.900; p=0.001), maximal workload (r=0.753; p=0.019) and steady state workload (r=0.928; p<0.001). ET increased maximal workload and muscle strength. In addition, ET lowered adiponectin mRNA expression (p=0.017), whereas the expression of AdipoR1 (p=0.011) and downstream metabolic genes was increased to levels comparable to those in healthy subjects. ELISA confirmed the normalisation of skeletal muscle adiponectin expression at the protein level (p=0.047).
Conclusion At the level of the skeletal muscle, CHF patients are characterised by increased adiponectin expression and decreased expression of AdipoR1 and downstream metabolic genes. ET normalises the mRNA expression of adiponectin and AdipoR1 and reverses disorders in lipid and glucose metabolism in skeletal muscle. These alterations in metabolic gene expression may help to understand the beneficial effects of ET in CHF.
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Funding This work was supported by the Fund for Scientific Research (FWO), Flanders (Belgium). AMVB is supported by a PhD fellowship, PB has been granted a special PhD fellowship and VMC is a Senior Clinical Investigator of the FWO, Flanders. RV-C is a senior scientist of the Centre National de la Recherche Scientifique.
Competing interest None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of Antwerp University Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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