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. IOC68_MiPNet17.08

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Lund J, Hafstad AD, Hagve M, Larsen TS, Aasum E (2012)

Event: 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 respiratory capacity (Vmax). Mitochondrial leak oxygen consumption (Voligo) was recorded after depletion of ADP and addition of oligomycin (4 µg/mL). In order to estimate the mitochondrial 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: Vmax was reduced and Voligo was increased in cardiac mitochondria from DIO mice. HIT was found to normalize Vmax and to cause an increase in Voligo. Palmitate was found to increase Voligo 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 respiratory 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 Tromso Larsen TS

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Organism: Mouse  Tissue;cell: Cardiac Muscle"Cardiac Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.  Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. 

HRR: Oxygraph-2k