Michael Rosenbaum

Abstract

The relative long-term stability of human energy stores suggest that energy intake and output are balanced at “usual” body weight and co-vary in a manner that maintains energy within a relatively narrow range. However, maintenance of a weight-reduced state in lean or obese individuals is characterized by a disproportionate decline in energy expenditure as well as a decrease in satiety and a relative increase in energy intake relative to expenditure. These metabolic and behavioral adjustments act coordinately to favor regain of lost weight, and are by and large reversed by the administration of “replacement” doses of exogenous leptin.

Using functional magnetic resonance imaging (fMRI), we have examined neural signaling in response to food versus non-food cues in subjects studied at their usual weight and during maintenance of a 10% reduced weight while receiving twice daily injections of either placebo or leptin. Following weight loss, there were predictable changes in neural activity, many of which were reversed by leptin, in brain areas known to be involved in the regulatory, emotional, and cognitive control of food intake. These changes were significantly and predictably correlated with behavioral changes in ingestive behavior and feelings of hunger and satiety following weight loss with and without leptin “replacement”. Furthermore, the weight loss and leptin-sensitive brain areas detected in subjects following weight loss are similar to those identified in subjects with congenital leptin-deficiency studied with and without exogenous leptin.

These data suggest that the weight-reduced state is “perceived” by leptin-sensitive CNS pathways as one of relative leptin deficiency resulting in coordinate changes in energy expenditure and intake that favor the regain of weight after otherwise successful weight reduction.

Biography

Michael Rosenbaum M.D. is Associate Program Director of the Clinical Research Center and Associate Clinical Professor of Pediatrics and Medicine at Columbia Presbyterian Medical Center. He received his B.A. in Neuroscience from Amherst College and M.D. from Cornell University. After a pediatric residency at Columbia Presbyterian Medical Center he completed a fellowship in endocrinology at The New York Hospital. Dr. Rosenbaum has authored numerous papers related to his research interests in human body weight regulation and the pathogenesis of obesity and type 2 diabetes. His work is supported by the NIH, AMDeC, and the Starr Foundation.