Holloway 2013 Abstract MiP2013

Holloway GP(2013) Tissue specific changes in respiratory substrate kinetics in the ZDF rat and in response to resveratrol supplementation. Mitochondr Physiol Network 18.08.

Link:

Holloway GP (2013)

Event: MiP2013

Mitochondrial dysfunction has been implicated in both high-fat diet induced skeletal muscle insulin resistance and diastolic heart failure. However there is considerable controversy regarding these concepts, as mitochondrial function has traditionally been assessed in the presence of saturating substrates (ADP and reducing equivalents), conditions which may not reflect the in vivo situation. Therefore, we investigated respiratory substrate kinetics in the heart and skeletal muscle in a model of type 2 diabetes, the ZDF rat. In addition, we determined the ability of the polyphenolic compound resveratrol to recover potentially impaired kinetic profiles in these tissues. Intriguingly, maximal respiration was not altered in either muscle in the ZDF rat, however tissue specific differences were observed in respiratory kinetics. Specifically, in skeletal muscle, submaximal ADP-stimulated respiration rates were lower (P<0.05) in ZDF rats, which coincided with decreased adenine nucleotide translocase 2 (ANT2) protein content. This decrease in submaximal ADP-stimulated respiration occurred in the absence of a decrease in electron transfer system function. Treating ZDF rats with resveratrol improved skeletal muscle insulin resistance and this was associated with increased submaximal ADP-stimulated respiration rates as well as an increase in ANT2 protein content. These results coincided with a greater ability of ADP to attenuate mitochondrial ROS emission and an improvement in cellular redox balance. In the heart, unlike skeletal muscle ADP kinetics were not altered by either genotype or resveratrol supplementation. In contrast, while P-CoA sensitivity was impaired (higher Km’) in the heart of ZDF rats, resveratrol normalized P-CoA kinetics, which coincided with a recovered diastolic function and myocardial lipid profile (TAG, DAG and ceramide species). Altogether, these data suggest that mitochondrial dysfunction is present in the skeletal muscle and heart of type 2 diabetic animals, and resveratrol improves bioenergetics by altering respiratory kinetics in a tissue specific manner.

• O2k-Network Lab: CA Guelph Holloway GP

Labels:

Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Rat  Tissue;cell: Heart, Skeletal muscle 

Enzyme: Adenine Nucleotide Translocase"Adenine Nucleotide Translocase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: Redox State"Redox State" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.  Coupling state: OXPHOS 

HRR: Oxygraph-2k 

Affiliations and author contributions

1 - Dept. Human Health and Nutritional Sciences, University of Guelph, ON, Canada

Email: ghollowa@uoguelph.ca