title: Exercise training boosts eNOS-dependent mitochondrial biogenesis in mouse heart: role in adaptation of glucose metabolism.
abstract: Endurance exercise training increases cardiac energy metabolism through poorly understood mechanisms. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) in cardiomyocytes contributes to cardiac adaptation. Here we demonstrate that the NO donor diethylenetriamine-NO (DETA-NO) activated mitochondrial biogenesis and function, as assessed by upregulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (Tfam) expression, and by increased mitochondrial DNA content and citrate synthase activity in primary mouse cardiomyocytes. DETA-NO also induced mitochondrial biogenesis and function and enhanced both basal and insulin-stimulated glucose uptake in HL-1 cardiomyocytes. The DETA-NO-mediated effects were suppressed by either PGC-1α or Tfam small-interference RNA in HL-1 cardiomyocytes. Wild-type and eNOS(-/-) mice were subjected to 6 wk graduated swim training. We found that eNOS expression, mitochondrial biogenesis, mitochondrial volume density and number, and both basal and insulin-stimulated glucose uptake were increased in left ventricles of swim-trained wild-type mice. On the contrary, the genetic deletion of eNOS prevented all these adaptive phenomena. Our findings demonstrate that exercise training promotes eNOS-dependent mitochondrial biogenesis in heart, which behaves as an essential step in cardiac glucose transport.
authors.affiliation: Internal Medicine Unit and Center for the Study and Integrated Treatment of Obesity, Department of Medicine, Padua University, Padua, Italy;
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Alessandra
authors.initials: A
authors.lastname: Valerio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ragni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trevellin
authors.forename: Marnie
authors.initials: M
authors.lastname: Granzotto
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Olivieri
authors.forename: Laura
authors.initials: L
authors.lastname: Tedesco
authors.forename: Chiara
authors.initials: C
authors.lastname: Ruocco
authors.forename: Andrea
authors.initials: A
authors.lastname: Fossati
authors.forename: Roberto
authors.initials: R
authors.lastname: Fabris
authors.forename: Roberto
authors.initials: R
authors.lastname: Serra
authors.forename: Michele O
authors.initials: MO
authors.lastname: Carruba
authors.forename: Enzo
authors.initials: E
authors.lastname: Nisoli
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology
chemical_list: C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C081930:Tfam protein, mouse; D014157:Transcription Factors; D014226:Triazenes; D052250:Nitric Oxide Synthase Type III; D005947:Glucose
keywords: endothelial nitric oxide synthase; exercise training; glucose uptake; heart; mitochondrial biogenesis; nitric oxide