Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice.
OBJECTIVE
To investigate the effect of SR141716, a selective CB1 receptor antagonist, on energy expenditure and on glucose uptake in isolated soleus muscle of Lep(ob)/Lep(ob) mice.


METHODS
Female Lep(ob)/Lep(ob) mice (8-10 weeks old) were treated with SR141716 (10 mg/kg, i.p. once daily) or vehicle for 7 days.


METHODS
Oxygen consumption, daily food and water intake, body weight and glucose uptake in isolated soleus muscle.


RESULTS
SR141716 (10 mg/kg, i.p. once daily) resulted in a significant reduction of daily food intake (P<0.01) and body weight (P<0.05) 5 days after daily treatment. Body weight continued to be lower for the rest of the treatment period (P<0.05). There was no significant difference in body weight between the pair-fed and vehicle-treated animals. A 7-day treatment with SR141716 (10 mg/kg, i.p. once daily) caused 37% increase in basal oxygen consumption compared to that of vehicle-treated (90 min mean; P<0.01), and a significant 68% increase in glucose uptake in isolated soleus muscle preparations.


CONCLUSIONS
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.
Liu
Y L
YL
Department of Physiology, Basic Medical Sciences, St George's Hospital Medical School, Tooting, London SW17 0RE, UK. yliu@sghms.ac.uk
Connoley
I P
IP
Wilson
C A
CA
Stock
M J
MJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D022722:Thermogenesis / Q000187:drug effects; D046509:Tissue Culture Techniques
D001786:Blood Glucose; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant