title: 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: Merck, Whitehouse Station, NJ, USA. Alison_Strack@merck.com
authors: Alison M
authors: AM
authors: Strack
authors: Susan
authors: S
authors: Nicolich
authors: Terry
authors: T
authors: Faidley
authors: Joana
authors: J
authors: Achanfuo-Yeboah
authors: Paul K
authors: PK
authors: Cunningham
authors: Donald
authors: D
authors: Hora
authors: Donald
authors: D
authors: Thompson
authors: Gerry
authors: G
authors: Hickey
authors: Amy O
authors: AO
authors: Johnson-Levonas
authors: Tung M
authors: TM
authors: Fong
authors: Steven B
authors: SB
authors: Heymsfield
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011897:Random Allocation; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects* / Q000502:physiology
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251