98-70811 BRONSON, F.H. The brain monitors body fatness by assessing the amount of leptin in circulation. Leptin is the protein product of a gene that is expressed only in fat cells. It has been hypothesized that leptin acts as a metabolic gate for puberty in females. That hypothesis stems from correlative studies and relates to an older and quite controversial hypothesis, namely that the pubertal ovulation cannot occur until energy stores are adequate to support pregnancy and lactation. A worry about both of these hypotheses is that they stem from experiments done in conditions that are exceptionally benign compared to those in which the relationship between leptin, fatness and ovulation actually evolved. The first specific aim of this proposal is to test these two hypotheses using wild house mice that are exposed to conditions that mimic those that wild animals experience in nature. The alternative hypotheses being offered here are (a) that a young female must be in positive energy balance in order to ovulate but that energy reserves per se are important only indirectly in that they are a component of the energy balancing process and thus (b) that leptin does not act as a metabolic gate for puberty. Numerous studies in a variety of laboratories have shown that circulating levels of leptin are important in regulating feeding behavior. The worry here again is that these studies have been done in oversimplified conditions and that the relationship between leptin and feeding behavior is much more complex that now thought. The second specific aim of this proposal is to test the hypothesis that the the effect of leptin on feeding behavior is actually only one component of its role in regulating the economics of foraging (calories gained vs. calories lost while foraging) This hypothesis will be tested using wild house that are exposed to the kinds of complex foraging conditions they would experience in the wild. Overall, the object of this proposal is to greatly clarify the relationship between energy balance, foraging behavior, leptin and puberty.
