Rimonabant prevents additional accumulation of visceral and subcutaneous fat during high-fat feeding in dogs.
We investigated whether rimonabant, a type 1 cannabinoid receptor antagonist, reduces visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in dogs maintained on a hypercaloric high-fat diet (HHFD). To determine whether energy expenditure contributed to body weight changes, we also calculated resting metabolic rate. Twenty male dogs received either rimonabant (1.25 mg.kg(-1).day(-1), orally; n = 11) or placebo (n = 9) for 16 wk, concomitant with a HHFD. VAT, SAT, and nonfat tissue were measured by magnetic resonance imaging. Resting metabolic rate was assessed by indirect calorimetry. By week 16 of treatment, rimonabant dogs lost 2.5% of their body weight (P = 0.029), whereas in placebo dogs body weight increased by 6.2% (P < 0.001). Rimonabant reduced food intake (P = 0.027), concomitant with a reduction of SAT by 19.5% (P < 0.001). In contrast with the VAT increase with placebo (P < 0.01), VAT did not change with rimonabant. Nonfat tissue remained unchanged in both groups. Body weight loss was not associated with either resting metabolic rate (r(2) = 0.24; P = 0.154) or food intake (r(2) = 0.24; P = 0.166). In conclusion, rimonabant reduced body weight together with a reduction in abdominal fat, mainly because of SAT loss. Body weight changes were not associated with either resting metabolic rate or food intake. The findings provide evidence of a peripheral effect of rimonabant to reduce adiposity and body weight, possibly through a direct effect on adipose tissue.
Dept. of Physiology, Keck School of Medicine, Univ. of Southern California, 1333 San Pablo St., MMR 626, Los Angeles, CA 90033, USA.
Joyce M
JM
Richey
Orison O
OO
Woolcott
Darko
D
Stefanovski
L Nicole
LN
Harrison
Dan
D
Zheng
Maya
M
Lottati
Isabel R
IR
Hsu
Stella P
SP
Kim
Morvarid
M
Kabir
Karyn J
KJ
Catalano
Jenny D
JD
Chiu
Viorica
V
Ionut
Cathryn
C
Kolka
Vahe
V
Mooradian
Richard N
RN
Bergman
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D004285:Dogs; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects* / Q000473:pathology
D004041:Dietary Fats; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant