Effects of orexins on energy balance and thermoregulation.

Intracerebroventricular injections of 10-20-microg orexin-A induce food intake in rats for about 30 min, or enhance fasting-induced hyperphagia. In thermoregulatory studies, an amount of 2 microg of the peptide causes hypometabolism and hypothermia in the same period. The thermoregulatory reaction can be demonstrated at moderately cool environments, mainly after slight food deprivation. Both the ingestive and the thermoregulatory reactions are more pronounced in cold-adapted animals. Pretreatment with D-Tyr27,36,D-Thr32-NPY(27-36), a peptide-antagonist of NPY, prevents the hypothermia. It is concluded that, probably through NPY activation, orexin-A is involved primarily in the regulation of energy status of the body (as an anabolic agent), and not simply in the regulation of either food intake or body temperature. This anabolic response is followed by a late and more sustained catabolic phase characterized by absence of food intake, increased metabolism and dose-dependent hyperthermia, which hyperthermia cannot be suppressed by the NPY-antagonist. In contrast to orexin-A, neither hyperphagia nor suppression of refeeding hyperphagia, but dose-dependent hyperthermia follows injections of orexin-B, suggesting that this peptide has neither coordinated anabolic nor coordinated catabolic effects on energy balance.