Submitted on December 8, 2008
Revised on March 23, 2009
Accepted on April 10, 2009
Rimonabant Prevents Additional Accumulation of Visceral and Subcutaneous Fat During High-Fat Feeding In Dogs
Joyce M. Richey1*, Orison O. Woolcott2, Darko Stefanovski3, L. Nicole Harrison2, Dan Zheng1, Maya Lottati2, Isabel R Hsu, Stella P Kim1, Morvarid Kabir1, Karyn J Catalano4, Jenny D. Chiu2, Viorica Ionut1, Cathryn Kolka2, Vahe Mooradian2, and Richard N. Bergman5
1 Keck School of Medicine of USC
2 University of Southern California
3 Keck School of Medicine, University of Southern California
4 Keck School of Medicine University of Southern California
5 University of Southern California Medical School
* To whom correspondence should be addressed. E-mail: jrichey{at}usc.edu.
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 · d-1, orally; n = 11) or placebo (n = 9) for 16 weeks, concomitant with a HHFD. VAT, SAT and non-fat 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), while 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. Non-fat tissue remained unchanged in both groups. Body weight loss was not associated with either resting metabolic rate (R2 = 0.24; P = 0.154) or food intake (R2 = 0.24; P = 0.166). In conclusion, rimonabant reduced body weight together with a reduction in abdominal fat, mainly due to 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.
