Exercise can induce temporary mitochondrial and contractile dysfunction linked to impaired respiratory chain complex activity

• Published in: Metabolism, clinical and experimental clinical and experimental, 2012, Vol.61 (1), p.117-126
• Main Authors: Schoepe, Maria, Schrepper, Andrea, Schwarzer, Michael, Osterholt, Moritz, Doenst, Torsten
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Respiration - genetics; Cell Respiration - physiology; Electron Transport - genetics; Electron Transport - physiology; Electron Transport Complex I - genetics; Electron Transport Complex I - metabolism; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; Endocrinology & Metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; GA-Binding Protein Transcription Factor - genetics; GA-Binding Protein Transcription Factor - metabolism; Heart - physiopathology; Male; Mitochondria - genetics; Mitochondria - metabolism; Mitochondria - physiology; Mitochondrial Diseases - genetics; Mitochondrial Diseases - metabolism; Muscle Contraction - genetics; Muscle Contraction - physiology; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Nuclear Respiratory Factor 1 - genetics; Nuclear Respiratory Factor 1 - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Ventricular Dysfunction, Left - genetics; Ventricular Dysfunction, Left - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2011.05.023

Abstract Exercise is considered to elicit a physiological response of the heart. Previous studies investigated the influence of repetitive exercise only at the end of the training period. We assessed the impact of 2 exercise protocols, differing in their treadmill inclination, on cardiac and mitochondrial function at different times during the training period. Within 10 weeks, animals trained with 16% incline developed hypertrophy (left ventricular posterior wall thickness: 1.6 ± 0.1 vs 2.4 ± 0.1 mm; P < .05) with normal function (ejection fraction: 75.2% ± 2.5% vs 75.6% ± 2.1%). However, at 6 weeks, there was temporary impairment of contractile function (ejection fraction: 74.5% ± 1.67% vs 65.8% ± 2.3%; P < .05) associated with decreased mitochondrial respiratory capacity (state 3 respiration: 326 ± 71 vs 161 ± 22 natoms/[min mg protein]; P < .05) and a gene expression shift from the adult ( α ) to the fetal ( β ) myosin heavy chain isoform. Although peroxisome proliferator-activated receptor gamma coactivator–1 α expression was normal, nuclear respiratory factors (NRFs)–1 and –2 were significantly reduced (NRF-1: 1.00 ± 0.16 vs 0.55 ± 0.09; NRF-2: 1.00 ± 0.11 vs 0.63 ± 0.07; P < .05) after 6 weeks. These findings were associated with a reduction of electron transport chain complexes I and IV activity (complex I: 1016 ± 67 vs 758 ± 71 nmol/[min mg protein]; complex IV: 18768 ± 1394 vs 14692 ± 960 nmol/[min mg protein]; P < .05). Messenger RNA expression of selected nuclear encoded subunits of the electron transport chain was unchanged at all investigated time points. In contrast, animals trained with 10% incline showed less hypertrophy and normal function in echocardiography, normal maximal respiratory capacity, and unchanged complex activities at all 3 time points. Repetitive exercise may cause contractile and mitochondrial dysfunction characterized by impaired respiratory chain complex activities. This activity reduction is temporary and intensity related.