Exercise Training Rescues Impaired Exercise Capacity in Mice With Systemic Deletion of Acetyl CoA carboxylase 2 (ACC2)

Fatty acids (FAs) are an important energy source for long duration endurance exercise. Mitochondrial uptake of (FAs) is inhibited by malonyl CoA, which is produced via the enzyme acetyl CoA carboxylase 2 (ACC2). In the present study, we generated mice with a systemic deletion of ACC2 (ACC2-null) to increase fatty acid oxidation (FAO) and promote endurance exercise capacity. Using metabolic chambers, the respiratory quotient during the initial hours of the dark cycle was lower in male ACC2-null mice, suggesting increased FAO. Body weight, as well as heart, skeletal muscle, liver, and adipose tissue mass in untrained ACC2-null mice were similar to control (CON). No differences in cage activity and food intake were noted between CON and ACC2-null mice. When subjected to an endurance exercise capacity (EEC) test on a motorized treadmill, ACC2-null mice showed a 25% decrease in EEC, which was associated with a ~20% reduction of citrate synthase (CS) activity in the soleus but not in liver and heart. Electron microscopy analysis suggested lower mitochondria density and abnormal size distribution in ACC2-null soleus muscle. However, 10 weeks of exercise training normalized the decreased EEC in ACC2-null mice and corrected the deficit in skeletal muscle CS activity. Systemic deletion of ACC2 impairs EEC in untrained mice, due to a negative effect on skeletal muscle mitochondria size and function. However, exercise training corrects this defect. The present data suggests that increasing mitochondrial FA transport, via ACC2 deletion, is not effective for improving exercise capacity and may negatively affect skeletal muscle mitochondria

The Effects of Ketogenic Diet on Type I Diabetes in Mice

Ketogenic diets and ketone body supplements are popular for combating obesity and improving weight loss or enhancing exercise performance, but the literature results are controversial. However, because the ketogenic diet is very low in carbohydrates, the diet could be an effective strategy for controlling blood glucose levels in type I diabetes. Therefore, the purpose of this study is to evaluate the effects of the ketogenic diet on type I diabetes in male mice. Twenty male mice were randomly assigned to control group or injected with streptozotocin (STZ) to induce type I diabetes. STZ mice were injected with 150 mg/kg body weight. After one week, control and STZ mice were randomly assigned to either chow or ketogenic diet for four weeks (n=5 in each group). Mice were weighed weekly to evaluate changes in body weight and blood glucose was checked at two-week intervals. At the end of four weeks, gravimetric analysis on heart, liver, and adipose tissue was performed to evaluate changes in organs due to diet. The findings of this pilot study could provide some insight into whether the ketogenic diet is a suitable intervention for type I diabetes

Exercise Training Rescues Impaired Exercise Capacity in Mice with Systemic Deletion of Acetyl CoA Carboxylase 2 (ACC2)

Fatty acids (FAs) are an important energy source for long duration endurance exercise. Mitochondrial uptake of (FAs) is inhibited by malonyl CoA, which is produced via the enzyme acetyl CoA carboxylase 2 (ACC2). In the present study, we generated mice with a systemic deletion of ACC2 (ACC2-null) to increase fatty acid oxidation (FAO) and promote endurance exercise capacity. Using metabolic chambers, the respiratory quotient during the initial hours of the dark cycle was lower in male ACC2-null mice, suggesting increased FAO. Body weight, as well as heart, skeletal muscle, liver, and adipose tissue mass in untrained ACC2-null mice were similar to control (CON). No differences in cage activity and food intake were noted between CON and ACC2-null mice. When subjected to an endurance exercise capacity (EEC) test on a motorized treadmill, ACC2-null mice showed a 25% decrease in EEC, which was associated with a ~20% reduction of citrate synthase (CS) activity in the soleus but not in liver and heart. Electron microscopy analysis suggested lower mitochondria density and abnormal size distribution in ACC2-null soleus muscle. However, 10 weeks of exercise training normalized the decreased EEC in ACC2-null mice and corrected the deficit in skeletal muscle CS activity. Systemic deletion of ACC2 impairs EEC in untrained mice, due to a negative effect on skeletal muscle mitochondria size and function. However, exercise training corrects this defect. The present data suggests that increasing mitochondrial FA transport, via ACC2 deletion, is not effective for improving exercise capacity and may negatively affect skeletal muscle mitochondria