Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lepob/Lepob mice

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Abstract
To investigate the effect of SR141716, a selective CB1 receptor antagonist, on energy expenditure and on glucose uptake in isolated soleus muscle of Lepob/Lepob mice. Female Lepob/Lepob mice (8–10 weeks old) were treated with SR141716 (10 mg/kg, i.p. once daily) or vehicle for 7 days. Oxygen consumption, daily food and water intake, body weight and glucose uptake in isolated soleus muscle. SR141716 (10 mg/kg, i.p. once daily) resulted in a significant reduction of daily food intake (PPPP<0.01), and a significant 68% increase in glucose uptake in isolated soleus muscle preparations. It is concluded that SR141716 has a direct effect on energy expenditure suggesting that the antiobesity effect of SR141716 is due to activation of thermogenesis in addition to the initial hypophagia. The increase in soleus muscle glucose uptake with SR141716 treatment may contribute to the improved glycaemia seen in the previous studies.