9309545 White One of the most basic needs of a complex organism is the maintenance of nutrient and energy homeostasis, a process which requires coordination of nutrient, hormonal, and neuronal signals to integrate metabolism with behavior. Food intake, appetite and body weight are controlled by the brain through an interaction with peripheral signals. This interaction is complex and poorly understood even though it is of obvious importance. Recently, it has been discovered that a peptide in the brain, neuropeptide Y, induces feeding when injected into specific nuclei of the hypothalamus. Indeed neuropeptide Y is one of the most abundant peptides and is one of the most potent stimulants of food intake in satiated mammals. During his previous NSF support, Dr. White demonstrated that neuropeptide Y is an integral link in the communication between the periphery and the brain for regulating energy homeostasis and food intake. He will now determine the means by which neuropeptide Y gene expression in the hypothalamus and pituitary is directly responsive to peripheral hormones regulating metabolism, i.e. insulin, glucocorticoids and thyroid hormone. Dr. White will examine how much neuropeptide Y is formed under various experimental conditions that manipulate peripheral hormone levels. These studies of neuropeptide Y gene regulation by the peripheral hormones will provide valuable information about the physiological role of this peptide in integrating metabolic signals important in energy homeostasis, food intake and body weight regulation with neuroendocrine function of the hypothalamus. These studies can serve as a basis for understanding how such regulatory systems become disturbed in physiologies such as obesity and anorexia nervosa and may lead to development of therapies for controlling human eating disorders. Indeed, Dr. White in collaboration with others in the Division of Endocrinology, submitted New Technology Disclosures for the use of specifi c diet formulations for the treatment of morbid obesity and for the stimulation of growth hormone secretion in growth hormone- suppressed individuals through the manipulations of specific brain neuropeptide systems. ***
