CB2 antagonism increases citrate synthase activity in slow oxidative skeletal muscle in a diet induced obese model (#85)
To determine the effects of pharmacological CB2 modulation on citrate synthase enzyme activity in slow oxidative and fast oxidative skeletal muscle in a diet induced model of obesity.
Male Sprague Dawley rats were fed a high fat diet (21%) ad libitum for 15 weeks. Obesity was achieved at nine weeks after which three treatment groups (n=9) were injected daily with either CB2 agonist AM1241 (3 mg/kg body weight) or CB2 antagonist AM630 (0.3 mg/kg body weight), or a control group injected with saline. 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 slow oxidative or fast oxidative fibre types. Citrate synthase activity was measured as a marker of functioning mitochondrial content.
Compared to control rats in both the CB2 antagonist and CB2 agonist treatment groups there was no significant difference in weight, body fat percentage and food intake. Citrate synthase activity was significantly increased (p=0.05) in the slow oxidative fibre types in the CB2 antagonist group but changes were not seen in fast oxidative skeletal muscle. No changes in citrate synthase activity were observed in either muscle in the CB2 agonist treatment group.
Six weeks of treatment with AM1241 (3 mg/kg body weight) or AM630 (0.3 mg/kg body weight) failed to achieve differences in body weight, body fat percentage and food consumption in a diet induced obese model . However in the CB2 antagonist group citrate synthase activity increased significantly implicating it as a potential oxidative therapeutic target.
Acknowledgments: This work was supported by funding from the Allen Foundation.