Appetite, Energy Expenditure, and the Regulation of Energy Balance

Conventional wisdom holds that "behavioral" issues related to the persistence of "bad habits" that provoke weight gain in the first place account for much or all of the virtually inexorable weight regain following dietary weight loss. However, the control of energy stores is achieved through coordinated regulation of energy intake and expenditure mediated by signals emanating from adipose, muscle, gastrointestinal, and other endocrine tissues, and integrated by the liver and by regulatory (hypothalamus, brain -stem), hedonic-emotional (amygdala, ventral striatum, orbitofrontal cortex), and executive-restraint (cingulate, middle frontal, supramarginal, precentral, and fusiform gyri) elements of the central nervous system (CNS). Changes in these signals are not voluntary and are largely due to the reduction in circulating leptin that accompanies a reduction in fat mass and is largely relived by the administration of "replacement" doses of exogenous leptin, and constitute the physiological basis for the high recidi-vism to obesity of otherwise successfully treated patients. For individuals successfully sustaining weight loss, the "price" is a lifetime of conscious effort to decrease energy intake and increase expenditure beyond the respective levels required of individuals who are "naturally" at the same weight. Considerations of therapy should be tempered by the fact that these responses are highly heterogeneous and that a "one-size-fits-all" approach to behavioral, surgical, or pharmacotherapeutic interventions is not likely to be successful.