Determining the effects of CB1 antagonism on skeletal muscle mitochondrial enzyme activity in different muscle fibre types in a diet induced obese model (#220)
CB1 antagonism has been shown to modulate both central and peripheral mechanisms. Abnormalities in skeletal muscle mitochondrial lipid and carbohydrate energy production have been shown to occur in obesity. The effects of CB1 antagonism on citrate synthase enzyme activity in type I (red) and type II (white) skeletal muscle is not known.
Male Sprague Dawley rats were fed a high fat diet (21%) ad libitum to induce obesity for 15 weeks. At nine weeks rats were injected daily with either CB1 antagonist AM251 (3 mg/kg body weight) or saline (n=9). Weight and food consumption were recorded daily. Body fat percentage was measured via magnetic resonance imaging at weeks 9 and 14. At 15 weeks the gastrocnemius muscle was removed and separated to red and white fibre types. Citrate synthase activity was measured as a marker of functioning mitochondrial content.
Compared to control the CB1 antagonist treatment group experienced significant weight loss at weeks 14 & 15 (p=0.0001). A significant decline in food consumption at 10 weeks (p=0.02) and a reduction in overall body fat percentage at week 15 (p=0.007). However citrate synthase activity did not alter in either the red or white muscle fibre types.
Despite significant decreases in body weight, food consumption and body fat percentage, citrate synthase activity did not alter between the different treatment groups. These results give further evidence to support CB1 antagonisms role in the reduction of body weight, food intake, and body fat mass.
Acknowledgments: This work was supported by funding from the Allen Foundation.