Cannabinoid-1 receptor inhibition prevents the reduction of 24-hour energy expenditure with weight loss.

Abstract

Pharmacologic inhibition of the cannabinoid-1 receptor (CB1R) in rodent models leads to weight loss and time-dependent changes in energy balance. This study evaluated the effects of CB1R inhibition on weight loss, energy expenditure (EE), and food intake (FI) in an obese canine model following 4 weeks of treatment. Eighteen maintenance-fed obese beagles were evenly and randomly allocated to a CB1R inverse agonist (AM251) (2 mg/kg), a 70% food-restricted (FR) diet, or a control group (C). Evaluations included body weight and composition (dual-energy x-ray absorptiometry scan), EE (doubly labeled water), and FI. Change in body mass at week 4 was significantly greater (P < .050) in the AM251 (-1476.7 g) and FR groups (-1100.0 g) than in the C group (-228.3 g). Food intake was decreased from week 2 onward in the FR and AM251 groups (P < .05). Absolute and lean mass-adjusted EEs were decreased only in the FR group (P < .01); EE in the AM251 group was greater (P < .05) than that in the FR group. Pharmacologic inhibition of CB1R in a canine model led to sustained effects on FI and EE. Weight loss was greater with AM251 than could be accounted for by food restriction (∼25%), an effect likely mediated by the EE response to CB1R inhibition.

• Authors: Alison M Strack, Susan Nicolich, Terry Faidley, Joana Achanfuo-Yeboah, Paul K Cunningham, Donald Hora Jr, Donald Thompson, Gerry Hickey, Amy O Johnson-Levonas, Tung M Fong, Steven B Heymsfield
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 61 Issue 4 Pg. 546-53 (Apr 2012) ISSN: 1532-8600 [Electronic] United States
• PMID: 22001334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Piperidines
• Pyrazoles
• Receptor, Cannabinoid, CB1
• AM 251

Topics

• Absorptiometry, Photon
• Animals
• Disease Models, Animal
• Dogs
• Eating (drug effects, physiology)
• Energy Metabolism (physiology)
• Female
• Glucose Tolerance Test
• Obesity (drug therapy, metabolism)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• Random Allocation
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors, metabolism)
• Weight Loss (drug effects, physiology)