PMID- 23162060 OWN - NLM STAT- MEDLINE DCOM- 20131021 LR - 20211021 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 10 IP - 3 DP - 2013 May TI - Impaired response to exercise intervention in the vasculature in metabolic syndrome. PG - 222-38 LID - 10.1177/1479164112459664 [doi] AB - 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 1alpha (PGC-1alpha) 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. FAU - Knaub, Leslie A AU - Knaub LA AD - Division of Endocrinology, Diabetes and Metabolism, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA. FAU - McCune, Sylvia AU - McCune S FAU - Chicco, Adam J AU - Chicco AJ FAU - Miller, Matthew AU - Miller M FAU - Moore, Russell L AU - Moore RL FAU - Birdsey, Nicholas AU - Birdsey N FAU - Lloyd, Monique I AU - Lloyd MI FAU - Villarreal, Juan AU - Villarreal J FAU - Keller, Amy C AU - Keller AC FAU - Watson, Peter A AU - Watson PA FAU - Reusch, Jane E B AU - Reusch JE LA - eng GR - R01 DK064741/DK/NIDDK NIH HHS/United States GR - UL1 RR025780/RR/NCRR NIH HHS/United States GR - HL14985/HL/NHLBI NIH HHS/United States GR - P01 HL014985/HL/NHLBI NIH HHS/United States GR - K12 HD057022/HD/NICHD NIH HHS/United States GR - UL1 TR001082/TR/NCATS NIH HHS/United States GR - I01 CX001532/CX/CSRD VA/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20121116 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 0 (Cytokines) RN - 0 (Ion Channels) RN - 0 (Mitochondrial Proteins) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppargc1a protein, rat) RN - 0 (RNA-Binding Proteins) RN - 0 (Transcription Factors) RN - 0 (Ucp3 protein, rat) RN - 0 (Uncoupling Protein 3) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos3 protein, rat) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - Aorta/immunology/metabolism/physiopathology MH - Blood Vessels/immunology/metabolism/*physiopathology MH - Cytokines/blood MH - *Disease Models, Animal MH - Hypertension/complications/metabolism/physiopathology/*therapy MH - Ion Channels/metabolism MH - Male MH - Metabolic Syndrome/etiology/*prevention & control MH - Mitochondria/enzymology/*metabolism MH - Mitochondrial Proteins/metabolism MH - *Motor Activity MH - Nitric Oxide Synthase Type III/metabolism MH - Obesity/complications/metabolism/physiopathology/*therapy MH - Oxidative Phosphorylation MH - Oxidative Stress MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MH - RNA-Binding Proteins/metabolism MH - Rats MH - Rats, Mutant Strains MH - Rats, Sprague-Dawley MH - Transcription Factors/metabolism MH - Uncoupling Protein 3 PMC - PMC4139293 MID - NIHMS602970 COIS- Conflict of interest None declared. EDAT- 2012/11/20 06:00 MHDA- 2013/10/22 06:00 PMCR- 2014/08/20 CRDT- 2012/11/20 06:00 PHST- 2012/11/20 06:00 [entrez] PHST- 2012/11/20 06:00 [pubmed] PHST- 2013/10/22 06:00 [medline] PHST- 2014/08/20 00:00 [pmc-release] AID - 1479164112459664 [pii] AID - 10.1177/1479164112459664 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2013 May;10(3):222-38. doi: 10.1177/1479164112459664. Epub 2012 Nov 16.