Wohlwend 2013 Thesis

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Wohlwend M (2013) Mitochondrial function in health and disease - high-resolution respirometry in rats inbred for high vs. low running capacity. Thesis Norwegian University of Science and Technology - Trondheim: 44pp.


Wohlwend M (2013) Thesis Norwegian University of Science and Technology - Trondheim

Abstract: Background: The mechanistically relation between low oxygen metabolism and poor health remains unresolved.

Methods: To pursue this aspect further, we measured mitochondrial oxidative phosphorylation (OXPHOS) capacity in permeabilized fibres of gastrocnemius (GASTRO) and left ventricle (LV) of the heart in 22 female rats artificially inbred for low- and high running capacity (LCR; HCR, respectively) for 30 generations. The rats were randomized to either sedate (LCRsed; HCRsed) or aerobic interval training (AIT) sessions 5 times a week for 1 month and then 2 times a week for 8 months (LCRext; HCRext).

Results: There was a significant effect of training and inbreeding on maximal oxygen uptake in these rats. Baseline results for GASTRO in LCRsed compared to HCRsed showed reduced fat oxidation, CI-, CII linked respiration and maximal OXPHOS (CI- and CII linked respiration). Activity of the TCA cycle enzyme citrate synthase (CS) was lower in LCR compared to HCR. Mitochondrial content independent calculations indicated an enzyme defect in β-oxidation, and that mitochondrial coupling efficiency of electron transfer during β-oxidation was impaired in LCRsed compared to HCRsed. AIT improved all these variables such that there was no difference in fat oxidation, CI-, CII linked respiration or maximal OXPHOS between LCRext and HCRext. These improvements were likely due to an increase in mitochondrial density, but also qualitative improvements particularly in fat oxidation (coupling efficiency and relative flux) were found. Baseline results for LV in LCRsed compared to HCRsed showed reduced CII linked respiration, maximal OXPHOS and similar activity of CS in LCRsed compared to HCRsed. Flux ratios as well as mitochondrial coupling efficiency during β-oxidation were similar between LCRsed and HCRsed. AIT improved maximal OXPHOS such that there was no difference between LCRext and HCRext. Interestingly, AIT had no effect on CS-activity in neither LCR nor HCR, suggesting primarily qualitative adjustments to exercise training in heart, mainly within β-oxidation and CII linked respiration. There was no dyscoupling effect as a result of phosphorylative constraint on electron transfer through complex I-IV by ATPsynthase in GASTRO or in LV, suggesting that ET-pathway rather than the phosphorylation system is limiting maximal ATP production in rats. Conclusions: Sedentary rats that contrast in intrinsic low- and high aerobic capacity differ significantly in OXHPOS, mitochondrial coupling efficiency and coupling control in GASTRO as well as in maximal OXPHOS in LV. Nine months of AIT was able to reverse all these initial impairments of mitochondrial function both in the heart and in the periphery, possibly through an interplay of different mechanisms. These findings might explain some of the poor health features of low capacity rats and suggest training-induced plasticity.

Keywords: Mitochondrial function, High-resolution respirometry, Oxygraph, Low/high aerobic capacity, Enzyme activity, Mitochondrial coupling efficiency, Fat oxidation, Heart, Skeletal muscle

O2k-Network Lab: NO Trondheim Rognmo O

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 

Organism: Rat  Tissue;cell: Heart, Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS  HRR: Oxygraph-2k