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November 14, 2002

Understanding hormones that regulate body weight

A baseball pitcher warming up in the bullpen, an actress’ understudy and an airplane copilot, are all back-ups capable of performing an essential function when needed. In human physiology, many of the body’s vital functions have at least one back-up system.

Dr. Michael Schwartz, professor of medicine and head of the Section of Clinical Nutrition in the Division of Metabolism, Endocrinology and Nutrition, and his colleagues are working to identify brain pathways that respond to two different hormones — leptin and insulin — that inform the brain biochemically about how much fat is in the body.

“Both leptin and insulin are produced in proportion to body fat mass,” says Schwartz. “Leptin is produced by fat cells and insulin by the pancreas. Although insulin is better known for its role in the control of blood sugar, both hormones signal the brain regarding the sufficiency of body fat content. When people lose weight, falling levels of these hormones stimulate appetite and promote the recovery of lost weight.”

Because of these adaptive responses, it is difficult for people to stick to a diet and keep weight off. The feelings of hunger dieters experience are likely due, at least in part, to reduced insulin and leptin signals. Conversely, when normal people overeat, an increase of leptin and insulin signaling in the brain helps them to eat less and lose the excess weight.

“Leptin sends a signal into brain cells that modifies their function,” says Schwartz. “Over the past couple of years, we have begun to focus on the nature of that cellular signal and its relationship to how these brain cells respond to insulin. Although receptors for leptin and insulin are quite different, we think that both hormones activate the same biochemical pathway in specific subsets of neurons that control food intake.”

In obese people, more leptin and insulin are produced and yet food consumption is typically normal or increased, suggesting that they may be leptin-resistant. The leptin-sensing regions of the brain are not responding appropriately to the leptin signal and this allows for an elevated level of body fat to be maintained and defended.

“We need to clearly understand exactly what these hormones are doing in the brain if we are to understand how this signaling system becomes deranged and leads to weight gain. This might ultimately lead to the development of drugs to maintain normal body weight.”

Schwartz presents the Nov. 21 Science in Medicine lecture, “Insulin, Leptin and the Hypothalamus: Key Components of the System Controlling Food Intake and Body Weight,” from noon to 1 p.m. in room D-209,Turner Auditorium, Health Sciences Center.

Schwartz earned a M.D. in 1983 from Rush Medical College in Chicago, where he received the Nathan M. Freer Award as the Outstanding Student of the Graduating Class. He first came to the UW in 1983 as a resident in medicine, completing a fellowship in endocrinology from 1987 to 1990. Schwartz was an acting instructor at the UW and then joined the faculty as assistant professor in 1993.

Among his numerous awards he received the Young Investigator Award of the American Federation for Medical Research in 1994, the Young Faculty Award of the Western Society for Clinical Investigation in 1995 and was elected to the American Society for Clinical Investigation in 1999.