Kotwica 2013 Abstract MiP2013

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Kotwica AO, Horscroft JA, Murray AJ(2013) Mitochondrial respiration in heart and soleus of ob/ob mice. Mitochondr Physiol Network 18.08.


Aleksandra Kotwica

MiP2013, Book of Abstracts Open Access

Kotwica AO, Horscroft JA, Murray AJ (2013)

Event: MiPNet18.08_MiP2013

In the West, obesity and type II diabetes (DM2) have reached epidemic proportions. The pathophysiological mechanisms behind these conditions are multifactorial, however recent evidence suggests that altered energy metabolism plays a key role in their development, with impaired cardiac and/or skeletal muscle respiratory capacity strongly implicated.

In this study, we aimed to compare mitochondrial respiratory function in the heart and skeletal muscle of 16 week old obese ob/ob mice and lean C57BL6 controls (N=8 per group). Muscle fibre bundles prepared from heart and soleus were permeabilised with saponin, and respirometry performed using Clark-type O2 electrodes, with a substrate-inhibitor titration used to determine ET-pathway function. Additionally, palmitoyl-carnitine+malate and pyruvate+malate were used to assess fat and carbohydrate oxidation, respectively.

In the hearts of ob/ob mice, LEAK respiration, (L) and OXPHOS capacity (P) via Complex I (CI) were the same as in lean controls (Fig. 1); however in soleus, ob/ob mice L through CI was 19% lower than in controls (p<0.05), whilst P was 30% lower (p<0.01). In both tissues, CII respiration rates were lower in ob/ob mice than in controls, by 18% in heart (p<0.05) and 35% in soleus (p<0.01). With pyruvate, cardiac L was 31% higher in ob/ob mice than controls (p<0.01), whilst maximal respiration was the same. In contrast, pyruvate respiration in the soleus of ob/ob mice was impaired, with L 18% lower (p<0.01) and P 47% lower (p<0.001) than in controls. With palmitoyl-carnitine, respiration rates were higher in both tissues of ob/ob mice than in controls, with cardiac L and P 51% (p<0.01) and 28% higher (p<0.05), respectively, and soleus L and P 38% (p<0.05) and 79% higher (p<0.01), respectively.

In conclusion, whilst fatty acid oxidation was elevated in both heart and soleus of ob/ob mice, compared with controls, there were soleus-specific defects in CI respiration, which may be a marker of oxidative stress. Our findings may suggest that skeletal muscle mitochondrial dysfunction in ob/ob mice precedes that of heart.

O2k-Network Lab: UK Cambridge Murray AJ

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression  Pathology: Obesity 

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

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


Affiliations and author contributions

Dept of Physiology, Development & Neuroscience, University of Cambridge, UK. - Email: aok24@cam.ac.uk