ROLE OF HYPOTHALAMIC NEUROPEPTIDE-Y NEURONS IN THE DEFECTIVE THERMOGENIC RESPONSE TO ACUTE COLD-EXPOSURE IN FATTY ZUCKER RATS

The fatty Zucker rat has impaired heat production and fails to mount a n adequate thermogenic response to cold exposure, partly because of de creased sympathetic drive to thermogenesis in brown adipose tissue. Ne uropeptide Y, synthesized in neurons of the hypothalamic arcuate nucle us and released in the paraventricular nucleus, stimulates feeding and inhibits brown adipose tissue activity. The neuropeptide Y neurons ar e overactive in fatty Zucker rats and are thought to contribute to hyp erphagia, reduced energy expenditure and obesity. We have examined the relationship between thermogenic activity in brown adipose tissue (me asured as uncoupling protein messenger RNA levels) and hypothalamic ne uropeptide Y and neuropeptide Y messenger RNA levels in response to co ld exposure (4 degrees C) for 2.5 and 18 h, in fatty and lean Zucker r ats. In lean Zucker rats, cold exposure at 4 degrees C for 2.5 and 18 h significantly increased uncoupling protein messenger RNA levels by 3 .5-fold (P<0.01) and 3.3-fold (P<0.01), respectively, compared with wa rm-maintained controls. Exposure to cold for 18 h also increased neuro peptide Y concentrations in the paraventricular nucleus (P<0.01) and v entromedial nucleus (P<O.OO1) in lean rats, with no change in neuropep tide Y messenger RNA after either 2.5 or 18 h. By contrast, fatty Zuck er rats showed no significant changes in uncoupling protein messenger RNA (P>0.05) at either duration of cold exposure. There were also no s ignificant changes in neuropeptide Y levels in any region nor in neuro peptide Y messenger RNA, with cold exposure for either period (P>0.05) . In lean rats, cold exposure therefore stimulates brown fat uncouplin g protein messenger RNA and also increases neuropeptide Y concentratio ns in its hypothalamic sites of release. We suggest that increased bro wn fat thermogenic capacity induced by cold in lean rats may be mediat ed, at least in part, by decreased neuropeptide Y release in the parav entricular nucleus, resulting in its accumulation in this site. Defect ive thermogenic responses in Fatty rats may result from central dysreg ulation of brown adipose tissue due to sustained and non-suppressible overactivity of hypothalamic neuropeptide Y neurons. (C) 1997 IBRO. Pu blished by Elsevier Science Ltd.