Analysis of Gene Expression in Hypothalamus in Obese and Normal Mice Using Differential Display

Obesity may result from increased calorie consumption, decreased energy expenditure, or both (1 ). These processes are controlled, at least in part, by the hypothalamus. Hypothalamic dysfunction is important in the development of obesity and it has long been known that lesions in the ventromedial hypothalamus lead to hyperphagia (2 ) and obesity, while lesions in the lateral hypothalamus impair the appetite response and lead to death by starvation. Neuropeptides that stimulate appetite such as NPY (3 ) and galanin, as well as neuropeptides that suppress appetite such as CRF (4 ), CCK (5 ), and GLP-1 (6 ) have been identified. However, understanding of the control of appetite remains incomplete. A key signal from the periphery, leptin, a hormone made in fat that regulates hypothalamic function, was only recently identified (7 ). While NPY is a potent stimulator of eating behavior, the NPY knockout mouse (8 ) exhibits a normal feeding phenotype, indicating that other factors are involved in the stimulation of hunger.