title: Obesity Downregulates MicroRNA-126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training.
abstract: Background.We investigated the effects of exercise training (ET) on miR-126 levels and skeletal muscle angiogenesis in obese Zucker rats.Results.Zucker rats were randomly assigned to sedentary and swimming-trained groups: lean sedentary (LS) and trained (LTR); obese sedentary (OB) and trained (OBTR). The OB group displayed capillary rarefaction compared with the LS group. In contrast, ET increased the capillary/fiber ratio by 38% in the LTR group and normalized capillary rarefaction in the OBTR group. VEGF, PI3K, and eNOS levels were reduced in the skeletal muscle of the OB group. ET normalized VEGF, PI3K, and eNOS levels in OBTR, contributing to vascular network homeostasis. PI3KR2 inhibits PI3K, a key mediator of the VEGF signaling pathway. Obesity decreased miR-126 and increased PI3KR2 levels compared with the LS group. However, ET normalized miR-126 levels in the OBTR group versus the LS group and decreased expression of PI3KR2.Conclusion.Our findings show that obesity leads to skeletal muscle capillary rarefaction, which is regulated by decreased miR-126 levels and increased PI3KR2. Inversely, ET normalizes miR-126 levels and VEGF signaling and should be considered an important therapeutic strategy for vascular disorders.
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: João Lucas Penteado
authors.identifier: 0000-0002-8374-2004
authors.initials: JL
authors.lastname: Gomes
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Fernandes
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Ursula Paula Reno
authors.initials: UP
authors.lastname: Soci
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: André Casanova
authors.initials: AC
authors.lastname: Silveira
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Diego Lopes Mendes
authors.initials: DL
authors.lastname: Barretti
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Negrão
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Edilamar Menezes
authors.identifier: 0000-0002-7101-312X
authors.initials: EM
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D001823:Body Composition / Q000502:physiology; D002196:Capillaries / Q000502:physiology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D015536:Down-Regulation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction; D013550:Swimming; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D002950:Citrate (si)-Synthase; D035683:MicroRNAs; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A