Metabolic Responses to Weight Perturbation

Abstract

The increasing prevalence of overweight and obesity is the cause of someof the largest and most costly current health care problems in theUnited States. This epidemic of obesity and its co-morbidities reflectsthe interaction of alleles of genes that favor the storage of excesscalories as fat with an environment that provides ad libitumavailability of calorically dense foods and encourages sedentarylifestyles. Almost anyone who has ever lost weight can attest to theobservation that it is harder to sustain weight loss than to loseweight. The over 80% recidivism rate to pre-weight loss levels of bodyfatness after otherwise successful weight loss is due to the coordinateactions of metabolic, behavioral, neuroendocrine, and autonomicresponses designed to keep body energy stores (fat) above a CNS-definedminimum. Much of this opposition to sustained weight loss is mediated bythe adipocyte-derived hormone, leptin.