Corticotropin releasing factor increases in brown adipose tissue thermogenesis and heart rate through dorsomedial hypothalamus and medullary raphe pallidus

Corticotropin releasing factor, acting at hypothalamic corticotropin releasing factor receptors, contributes to the neural signaling pathways mediating stress-related responses, as well as those involved in maintaining energy balance homeostasis. Sympathetically-regulated lipid metabolism and heat production in brown adipose tissue contributes to the non-shivering thermogenic component of stress-evoked hyperthermia and to energy expenditure aspects of body weight regulation. To identify potential central pathways through which hypothalamic corticotropin releasing factor influences brown adipose tissue thermogenesis, corticotropin releasing factor was microinjected into the lateral ventricle (i.c.v.) or into hypothalamic sites while recording sympathetic outflow to brown adipose tissue, brown adipose tissue temperature, expired CO₂, heart rate and arterial pressure in urethane/chloralose-anesthetized, artificially-ventilated rats. I.c.v. corticotropin releasing factor or corticotropin releasing factor microinjection into the preoptic area or the dorsomedial hypothalamus, but not the paraventricular nucleus of the hypothalamus, elicited sustained increases in brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature, expired CO₂ and heart rate. These sympathetic responses to i.c.v. corticotropin releasing factor were eliminated by inhibition of neuronal activity in the dorsomedial hypothalamus or in the raphe pallidus, a putative site of sympathetic premotor neurons for brown adipose tissue, and were markedly reduced by microinjection of ionotropic glutamate receptor antagonists into the dorsomedial hypothalamus. The increases in brown adipose tissue sympathetic outflow, brown adipose tissue temperature and heart rate elicited from corticotropin releasing factor into the preoptic area were reversed by inhibition of neuronal discharge in dorsomedial hypothalamus. These data indicate that corticotropin releasing factor release within the preoptic area activates a sympathoexcitatory pathway to brown adipose tissue and to the heart, perhaps similar to that activated by increased prostaglandin production in the preoptic area, that includes neurons in the dorsomedial hypothalamus and in the raphe pallidus.