The objective is to elucidate the physiological processes underlying the regulation of body energy. Of particular interest are the mechanisms responsible for setting the particular level to which energy is regulated, the adjustments in energy expenditure used to defend this level, and the means by which this regulated energy level might be altered. The present proposal has three specific goals. One is to extend ongoing investigations of hypothalamic and genetically obese (Zucker) rats aimed at pinpointing regulatory deficits underlying their obesity. Using metabolic indices, we will determine whether energy is normally regulated by these rats or whether their obesity reflects regulatory failure. If their capacity to regulate energy expenditure is impaired, we will attempt to characterize the regulatory dysfunctions responsible for their obesity. Secondly, we will seek cliniclly-relevant means of altering the regulated level of body energy. Some weight loss (e.g., diet-induced) is resisted by energy-conserving metabolic ajdustments characeristic of an organism in negative energy balance. In other cases (e.g., exercise-induced weight loss), energy flux is apparently normal, though at a reduced body weight. This raises the possibility that the regulated energy level has been reduced. Certain anorectic drugs, the gonadal hormone estrogen, and nicotine may similarly effect weight loss through primary shifts in energy homeostasis. By studying energy expenditure, we propose to determine whether the weight changes produced in rats by these variables involve primary shifts in regulated body energy. Thirdly, we propose experiments which examine the relation of carcass protein regulation to that of carcass energy. We will rely on the presence of regulatory responses to nitrogen perturbation to learn how carcass nitrogen is regulated and to establish criteria for determining when nitrogen stasis is achieved. Using these procedures, we will determine if disturbances in carcass nitrogen contribute to the obesity displayed by hypothalamic and Zucker obese rats. Our primary goal in studying carcass nitrogen is to understand energy regulation. By studying the effects of carcass nitrogen perturbations on energy regulation we hope that explanations will emerge for anomalies in carcass energy regulation.
