title: Exercise training reverses adiponectin resistance in skeletal muscle of patients with chronic heart failure.
abstract: 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 VO(2) 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: An M
authors.initials: AM
authors.lastname: Van Berendoncks
authors.forename: Anne
authors.initials: A
authors.lastname: Garnier
authors.forename: Paul
authors.initials: P
authors.lastname: Beckers
authors.forename: Vicky Y
authors.initials: VY
authors.lastname: Hoymans
authors.forename: Nadine
authors.initials: N
authors.lastname: Possemiers
authors.forename: Dominique
authors.initials: D
authors.lastname: Fortin
authors.forename: Viviane
authors.initials: V
authors.lastname: Van Hoof
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
authors.forename: Christiaan J
authors.initials: CJ
authors.lastname: Vrints
authors.forename: Renée
authors.initials: R
authors.lastname: Ventura-Clapier
authors.forename: Viviane M
authors.initials: VM
authors.lastname: Conraads
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D016022:Case-Control Studies; D002908:Chronic Disease; D015536:Down-Regulation; D005081:Exercise Therapy; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism*
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D012333:RNA, Messenger; D054419:Receptors, Adiponectin