WIDESPREAD INCREASES IN REGIONAL HYPOTHALAMIC NEUROPEPTIDE-Y LEVELS IN ACUTE COLD-EXPOSED RATS

Neuropeptide Y injected into the hypothalamus or third ventricle stimulates feeding and inhibits the sympathetic activation of brown adipose tissue. To clarify the involvement of hypothalamic neuropeptide Y in cold-induced thermogenesis, groups of rats exposed to 4-degrees-C for 2.5 or 18 h were compared with warm-adapted rats (22-degrees-C). Neuropeptide Y was measured in eight selected hypothalamic regions, including those known to be involved in the regulation of energy expenditure. Activation of brown adipose tissue was confirmed by significant six- to nine-fold increases in brown adipose tissue uncoupling protein messenger RNA. Compared with warm-adapted controls, neuropeptide Y levels were significantly raised by 80-170% in several hypothalamic regions of rats exposed to cold for 2.5 h, namely the medial preoptic area, paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus and lateral hypothalamic area. Neuropeptide Y levels in 18-h cold-exposed rats were similarly elevated in these regions and were also significantly increased in the anterior hypothalamic area (75%). By contrast, neuropeptide Y levels in the arcuate nucleus, the main hypothalamic site of synthesis, were not increased by cold exposure, being significantly reduced by 21% after 2.5 h exposure and comparable with controls after 18 h. As neuropeptide Y injection inhibits brown adipose tissue activation, we suggest that the rapid and dramatic increases in neuropeptide Y levels in specific hypothalamic regions occur because cold exposure might inhibit the release of neuropeptide Y and so cause accumulation of neuropeptide Y in these sites. By removing a central neuropeptide Y-ergic inhibitory influence on the sympathetic outflow to brown adipose tissue, such changes may lead to increased energy expenditure. At normal environmental temperatures, neuropeptide Y may therefore tonically inhibit brown adipose tissue activity to maintain body temperature and regulate energy homeostasis.