Impaired response to exercise intervention in the vasculature in metabolic syndrome

Diab Vasc Dis Res. 2013 May;10(3):222-38. doi: 10.1177/1479164112459664. Epub 2012 Nov 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Aorta / immunology
  • Aorta / metabolism
  • Aorta / physiopathology
  • Blood Vessels / immunology
  • Blood Vessels / metabolism
  • Blood Vessels / physiopathology*
  • Cytokines / blood
  • Disease Models, Animal*
  • Hypertension / complications
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Hypertension / therapy*
  • Ion Channels / metabolism
  • Male
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / prevention & control*
  • Mitochondria / enzymology
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism
  • Motor Activity*
  • Nitric Oxide Synthase Type III / metabolism
  • Obesity / complications
  • Obesity / metabolism
  • Obesity / physiopathology
  • Obesity / therapy*
  • Oxidative Phosphorylation
  • Oxidative Stress
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA-Binding Proteins / metabolism
  • Rats
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley
  • Transcription Factors / metabolism
  • Uncoupling Protein 3

Substances

  • Cytokines
  • Ion Channels
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • RNA-Binding Proteins
  • Transcription Factors
  • Ucp3 protein, rat
  • Uncoupling Protein 3
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • AMP-Activated Protein Kinases