Pharmacological blockade of the endocannabinoid system via rimonabant (SR141716) induced a sustained reduction in weight and fatness. Rimonabant-treated mice exhibited reduced metabolizable energy intake and increased daily energy expenditure on days 4-6 of treatment. However, these on the energy budget had disappeared by day 22-24. Rimonabant treatment increased daily physical activity levels throughout the study. These data suggested that rimonabant caused a negative energy balance by acting on both energy intake and expenditure. Melanin-concentrating receptor 1 (MCHR1) antagonism via GW803430 produced similar effects on energy  budget. However, only physical activity during the dark phase was increased by GW803430 treatment. MCHR1 antagonism produced a persistent anti-obesity effect and the initiation of weight loss resulted from a decrease in energy intake and an increase in active energy expenditure. With respect to environmental interventions, non-genetic individual variability in weightgain when fed a high fat diet (HFD) was investigated. I found that weight gain induced by HFD was associated positively with fat mass and fast free mass and negatively with physical activity prior to HFD exposure. Furthermore, fat mass and fat free mass were influenced by lactation litter size via weaning weight and post-weaning growth rate. Finally I used intermittent starvation to test whether the risk of starvation determines the lower intervention point as suggested by the dual intervention pointmodel. Overall, mice exhibited different behavioural and physiological responses to intermittent starvation dependent of the duration of treatment. This work contributes to a better understanding of the regulation of energy balance and provide useful insights for the prevention and treatment of obesity.

Thesis (Ph. D.)--State University of New York at Binghamton, Decker School of Nursing, 2008. / Includes bibliographical references.