Lund 2012 Abstract IOC68
|Lund J, Hafstad AD, Hagve M, Larsen TS, Aasum E (2012) High intensity exercise prevents impairment of respiratory capacity in cardiac mitochondria from obese mice. MiPNet17.08.|
Link: MiPNet17.08 IOC68
Cardiac inefficiency and increased myocardial oxygen consumption are hallmarks of diabetes-induced cardiomyopathy, and is most likely related to ROS generation and mitochondrial dysfunction. We have recently shown that exercise prevent development of cardiac dysfunction and inefficiency. In the present study we investigated the effect of high intensity training (HIT) on mitochondrial respiration in cardiac mitochondria from obese mice. Because long chain fatty acids are supposed to increase LEAK oxygen consumption, experiments were performed both in the absence and presence of albumin-bound palmitate.
Methods: Diet-induced obese (DIO) mice were obtained by feeding C57BL/6J mice a high fat diet for 8 weeks. DIO mice were thereafter subjected to either a sedentary lifestyle (SED) or HIT (interval running, 10x4 min at 85-95% of VO2max) for 8-10 weeks. Sedentary mice fed normal chow were included as lean controls (CON). Mitochondrial oxygen consumption was measured in isolated myocardial mitochondria (Oxygraph-2k, Oroboros Instruments) with glutamate and malate as substrates (5 and 2.5 mM, respectively). ADP (300 µM) was added to achieve maximal mitochondrial OXPHOS capacity (P). Mitochondrial LEAK oxygen consumption (L) was recorded after depletion of ADP and addition of oligomycin (4 µg/mL). In order to estimate the mitochondrial proton leak through the adenine nucleotide translocator (ANT), atractyloside (25 µM) was also added. The protocol was performed in the presence and absence of 75 μM palmitate.
Results: P was reduced and L was increased in cardiac mitochondria from DIO mice. HIT was found to normalize P and to cause an increase in L. Palmitate was found to increase L in all groups, although the latter response was less pronounced in mitochondria from HIT mice. Both basal and palmitate-dependent mitochondrial uncoupling was reduced by ANT inhibition.
Conclusion: Diet-induced obesity is associated with a reduction in cardiac mitochondrial OXPHOS capacity, while mitochondrial uncoupling was unaltered. Exercise training restored respiratory capacity and increased uncoupling in isolated cardiac mitochondria from obese mice. Exercise was also found to reduce the long chain fatty acid-induced uncoupling.
• Keywords: Exercise training, Respiration, Isolated mitochondria, Heart muscle, Obesity
• O2k-Network Lab: NO Tromsoe Larsen TS
Organism: Mouse Tissue;cell: Heart Preparation: Isolated mitochondria
Regulation: Fatty acid