Holloway 2013 Abstract MiP2013

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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.

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Graham Holloway

MiP2013, Book of Abstracts Open Access

Holloway GP (2013)

Event: MiPNet18.08_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-pathway 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.

Keywords: Pyruvate and P-CoA

O2k-Network Lab: CA Guelph Holloway GP


Labels: MiParea: Respiration, Genetic knockout;overexpression, Comparative MiP;environmental MiP, Pharmacology;toxicology  Pathology: Diabetes, Obesity  Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Heart, Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Adenine nucleotide translocase  Regulation: ADP, Redox state, Substrate  Coupling state: OXPHOS 

HRR: Oxygraph-2k 

MiP2013 

Affiliations and author contributions

Dept Human Health and Nutritional Sciences, University of Guelph, ON, Canada. - Email: ghollowa@uoguelph.ca