Jeffrey M. FriedmanMD, PhD
Dr. Friedman studies the molecular mechanisms that regulate food intake and body weight. He explores the mechanisms by which the hormone leptin controls feeding behavior, and he works to identify other key regulators of body weight.
Leptin is a hormone secreted by adipose (fat) tissue in proportion to its mass that in turn modulates food intake relative to energy expenditure. Increased fat mass increases leptin levels, which in turn reduces body weight; decreased fat mass leads to a decrease in leptin levels and an increase in body weight. By this mechanism, weight is maintained within a relatively narrow range. Defects in the leptin gene are associated with severe obesity in animals and in humans.
Leptin acts on sets of neurons in brain centers that control energy balance to regulate appetite. Leptin also plays a general role in regulating many of the physiologic responses that are observed with changes in nutritional state, with clear effects on female reproduction, immune function, and the function of many other hormones, including insulin.
The recent identification of the hypothalamic cells that express the leptin receptor is enabling Dr. Friedman and his colleagues to delineate the precise neuronal effects of leptin and the mechanisms by which this single molecule can alter a complex behavior. Recent studies have revealed that leptin reduces food intake by decreasing the pleasure associated with food. Dr. Friedman’s lab has identified a specific neural population in the hypothalamus that expresses a bioactive peptide known as MCH, which plays a key role in sensing the reward value of food. His ongoing studies seek to understand how leptin modulates the activity of these neurons as well as to identify additional neural populations that regulate feeding.