Regulation of energy balance by peptides: a review.

Regulation of energy balance consists of two intertwined circuitries: food intake-- metabolic rate--body weight, vs. metabolic rate--heat loss--body temperature. Metabolic rate serves interaction between the two. Some peptides influence individual components of energy homeostasis, without having coordinated anabolic or catabolic properties. Anabolic and catabolic peptides function with redundancy, and also show specific features. They all influence ingestive behavior vs. metabolic rate and temperature, but do not necessarily act directly at central thermoregulatory pathways. Most of them alter metabolic rate (but not heat loss) through the ventromedial nucleus, while consequent moderate changes in thermal signals can influence function of the preoptic/anterior hypothalamic region and initiate compensating regulatory steps to restore temperature. Thus, besides ingestion, these peptides influence metabolic rate, whereas the passive temperature changes will only be obvious as long as environmental circumstances allow. Other substances cause coordinated central regulatory changes resembling fever (e.g. cholecystokinin), anapyrexia, or cold-defense: they primarily affect body temperature, and then the temperature-dependent changes in catabolic/anabolic peptide functions alter feeding behavior. Such arrangement can secure relative independence of the two regulatory circles, allowing for minimization of depression in metabolic rate and body temperature during starvation (despite elevated anabolic activity), or for increased food intake with lack of hypothermia in cold adaptation (despite high anabolic activity), or for normal body temperature in overfed states (despite enhanced catabolic activity), etc. However, the independence is relative since the two systems interact in the overall regulation of energy homeostasis: neuropeptides influence body temperature and temperature modifies peptide actions.