Kotwica 2013 Abstract MiP2013
|Kotwica AO, Horscroft JA, Murray AJ(2013) Mitochondrial respiration in heart and soleus of ob/ob mice. Mitochondr Physiol Network 18.08.|
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
Dept of Physiology, Development & Neuroscience, University of Cambridge, UK. - Email: email@example.com