Metabolic and Endocrine Control of Behavior

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PI: Schneider, J. IBN-9723938 Many people overeat and gain too much weight, while other people eat too little and experience serious problems such as malnutrition and infertility. Leptin is a newly discovered protein that is naturally made and secreted by body fat cells, and is thought to play a role in the regulation of eating, body weight and fertility. This proposal is designed to understand how leptin influences eating, body weight and reproduction. We will study Syrian hamsters because, unlike other animals, they have a reliable, 4-day ovulatory (estrous) cycle that is very sensitive to leptin treatment, a short period of fasting, and increased exercise. We will look for clues as to where in the body and by what mechanism leptin affects body weight, eating and estrous cycles. For example, in order to find where leptin acts, we will compare the effects of leptin injected into the body to effects when leptin treatment is restricted to a small area of the brain. Some of the effects we will examine will be body weight, food intake and length of the estrous cycle. We will also treat hamsters with leptin and determine which parts of the brain become active. In addition, we will determine whether particular parts of the brain are critical for leptin's effects by examining the effects of leptin in hamsters with small lesions of these exact brain areas. Knowledge of leptin's mechanism and site of action may provide important clues to how body weight, eating and fertility are regulated as well as how to treat obesity or anorexia nervosa. This work may have more general importance for understanding a variety of behavioral problems that involve effects of metabolism on the nervous system.