Metabolic Responses to Weight Perturbation

The increasing prevalence of overweight and obesity is the cause of some of the largest and most costly current health care problems in the United States. This epidemic of obesity and its co-morbidities reflects the interaction of alleles of genes that favor the storage of excess calories as fat with an environment that provides ad libitum availability of calorically dense foods and encourages sedentary lifestyles. Almost anyone who has ever lost weight can attest to the observation that it is harder to sustain weight loss than to lose weight. The over 80% recidivism rate to pre-weight loss levels of body fatness after otherwise successful weight loss is due to the coordinate actions of metabolic, behavioral, neuroendocrine, and autonomic responses designed to keep body energy stores (fat) above a CNS-defined minimum. Much of this opposition to sustained weight loss is mediated by the adipocyte-derived hormone, leptin.