title: Impaired response to exercise intervention in the vasculature in metabolic syndrome.
abstract: Physical activity decreases risk for diabetes and cardiovascular disease morbidity and mortality; however, the specific impact of exercise on the diabetic vasculature is unexamined. We hypothesized that an acute, moderate exercise intervention in diabetic and hypertensive rats would induce mitochondrial biogenesis and mitochondrial antioxidant defence to improve vascular resilience. SHHF/Mcc-fa(cp) lean (hypertensive) and obese (hypertensive, insulin resistant), as well as Sprague Dawley (SD) control rats were run on a treadmill for 8 days. In aortic lysates from SD rats, we observed a significant increase in subunit proteins from oxidative phosphorylation (OxPhos) complexes I-III, with no changes in the lean or obese SHHF rats. Exercise also increased the expression of mitochondrial antioxidant defence uncoupling protein 3 (UCP3) (p < 0.05) in SHHF lean rats, whereas no changes were observed in the SD or SHHF obese rats with exercise. We evaluated upstream signalling pathways for mitochondrial biogenesis, and only peroxisome proliferators-activated receptor gamma coactivator 1α (PGC-1α) significantly decreased in SHHF lean rats (p < 0.05) with exercise. In these experiments, we demonstrate absent mitochondrial induction with exercise exposure in models of chronic vascular disease. These findings suggest that chronic vascular stress results in decreased sensitivity of vasculature to the adaptive mitochondrial responses normally induced by exercise.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Knaub
authors.forename: Sylvia
authors.initials: S
authors.lastname: McCune
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Chicco
authors.forename: Matthew
authors.initials: M
authors.lastname: Miller
authors.forename: Russell L
authors.initials: RL
authors.lastname: Moore
authors.forename: Nicholas
authors.initials: N
authors.lastname: Birdsey
authors.forename: Monique I
authors.initials: MI
authors.lastname: Lloyd
authors.forename: Juan
authors.initials: J
authors.lastname: Villarreal
authors.forename: Amy C
authors.initials: AC
authors.lastname: Keller
authors.forename: Peter A
authors.initials: PA
authors.lastname: Watson
authors.forename: Jane E B
authors.initials: JE
authors.lastname: Reusch
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000517:prevention & control*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009043:Motor Activity; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D000071247:Uncoupling Protein 3
chemical_list: D016207:Cytokines; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D055372:AMP-Activated Protein Kinases