Effects of chronic oral rimonabant administration on energy budgets of diet-induced obese C57BL/6 mice.
ABSTRACT The endocannabinoids have been recognized as an important system involved in the regulation of energy balance. Rimonabant (SR141716), a selective inverse agonist of cannabinoid receptor 1 (CB1), has been shown to cause weight loss. However, its suppressive impact on food intake is transient, indicating a likely additional effect on energy expenditure. To examine the effects of rimonabant on components of energy balance, we administered rimonabant or its vehicle to diet-induced obese (DIO) C57BL/6 mice once daily for 30 days, by oral gavage. Rimonabant induced a persistent weight reduction and a significant decrease in body fatness across all depots. In addition to transiently reduced food intake, rimonabant-treated mice exhibited decreased apparent energy absorption efficiency (AEAE), reduced metabolizable energy intake (MEI), and increased daily energy expenditure (DEE) on days 4-6 of treatment. However, these effects on the energy budget had disappeared by days 22-24 of treatment. No chronic group differences in resting metabolic rate (RMR) or respiratory quotient (RQ) (P > 0.05) were detected. Rimonabant treatment significantly increased daily physical activity (PA) levels both acutely and chronically. The increase in PA was attributed to elevated activity during the light phase but not during the dark phase. Taken together, these data suggested that rimonabant caused a negative energy balance by acting on both energy intake and expenditure. In the short term, the effect included both reduced intake and elevated PA but the chronic effect was only on increased PA expenditure.
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ABSTRACT: Obesity represents one of the most urgent global health threats as well as one of the leading causes of death throughout industrialized nations. Efficacious and safe therapies remain at large. Attempts to decrease fat mass via pharmacological reduction of energy intake have had limited potency or intolerable side effects. Increasingly widespread sedentary lifestyle is often cited as a major contributor to the increasing prevalence of obesity. Moreover, low levels of spontaneous physical activity (SPA) are a major predictor of fat mass accumulation during overfeeding in humans, pointing to a substantial role for SPA in the control of energy balance. Despite this, very little is known about the molecular mechanisms by which SPA is regulated. The overview will attempt to summarize available information on neuroendocrine factors regulating SPA.Journal of Nutrition 06/2005; 135(5):1314-9. · 4.20 Impact Factor
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ABSTRACT: Marijuana and its major psychotropic component, Delta(9)-tetrahydrocannabinol, stimulate appetite and increase body weight in wasting syndromes, suggesting that the CB(1) cannabinoid receptor and its endogenous ligands, the endocannabinoids, are involved in controlling energy balance. The endocannabinoid system controls food intake via both central and peripheral mechanisms, and it may also stimulate lipogenesis and fat accumulation. Here we discuss the multifaceted regulation of energy homeostasis by endocannabinoids, together with its applications to the treatment of eating disorders and metabolic syndromes.Nature Neuroscience 06/2005; 8(5):585-9. · 15.25 Impact Factor
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ABSTRACT: The maximum rate of sustained energy intake (SusEI) may limit reproductive effort and other aspects of animal performance. We have previously suggested that lactating mice are not limited centrally by the alimentary tract or peripherally by the mammary glands, but that the limits to SusEI are imposed by the capacity of the animal to dissipate body heat generated as a by-product of processing food and producing milk. To explore the nature of the limits to SusEI, we bred MF1 laboratory mice at 21 degrees C and then dorsally shaved lactating females to reduce their external insulation and thereby elevate their capacity to dissipate body heat. These mice increased their food intake by 12.0% and assimilated on average 30.9 kJ day(-1) more energy than unshaved animals. With nearly identical mean litter sizes (11.4 pups for shaved and 11.3 pups for unshaved mice), shaved mothers exported 15.2% (22.0 kJ day(-1)) more energy as milk than control individuals. The elevated milk production of shaved mice enabled them to wean litters that were 15.4% (12.2 g) heavier than offspring produced by unshaved mice. Our results argue against central, peripheral or extrinsic limits to SusEI at peak lactation and provide strong support for the heat dissipation limit hypothesis. More generally, we see many situations where heat dissipation may be a previously unrecognised factor constraining the evolution of endothermic animals - for example, the latitudinal and altitudinal trends in clutch and litter sizes and the migration patterns of birds.Journal of Experimental Biology 01/2008; 210(Pt 23):4233-43. · 3.24 Impact Factor