Neuroendocrinology of hyperphagias and obesities.

The energy balance of an adult in stable conditions and eating ad libitum is in equilibrium over a long term as well as just during the 24 hrs period. The activity phase of an individual may be diurnal or nocturnal, depending on the species ; this phase corresponds to relative hyperphagia and storage of the metabolites ingested but not used to cover continuous energy expenditure. During the resting phase, a compensatory process includes hypophagia and mobilization of the previously stored metabolites. The energy ballast is mainly represented by the adipose tissue, a store normally partly mobilized and reconstituted alternately. This metabolic pattern results from a neuroendocrine sequence whose partly known mechanism is the basis of the liporegulatory process. Obesity is caused by the alteration of this physiological mechanism regulating the adipose mass. Two factors seem to be the key to the very complex syndrome of hypothalamic obesityFirst, after lesion the feeding and metabolic light-dark cycle is abolished (the resting phase, hypophagia and lipolysis disappear) ; second, the cephalic phase of prandial events and particularly of insulin secretion is greatly enhanced. Works on this subject strongly suggest that hypothalamic lesion causes parasympathetic-sympathetic imbalance. In the normal resting animal, the stores are mobilized mainly by the sympathetic nervous system ; lower sympathetic activity in the lesioned animal would explain the absence of store mobilization. Increased parasympathetic activity would stimulate excessive preabsorptive insulin secretion under vagal control, producing the hyperinsulinemia characteristic of these animals. Recessive genetic obesities are due to a simple molecular variation in the DNA sequence coding a peptide which may be an enzyme or a structure protein. The recent hypothesis proposing that the genetic deficiency of ob/ob mice is due to defective regulation of thyroiddependent (Na +K)-ATP se is satisfying because it explains most of the metabolic and behavioral deviations described in those animals, particularly hyperinsulinemia. The mechanism eliciting dietetic obesity has not been extensively studied. A probable,