Synergistic action by neuropeptide Y (NPY) and norepinephrine (NE) on food intake, metabolic rate, and brown adipose tissue (BAT) causes remarkable weight loss in the obese (fa/fa) Zucker rat.

NPY has been reported to co-exist within catecholaminergic neurons of the central and peripheral nervous systems. The functional significance in noradrenergic neurons has been related to the vasomotor effects of NPY which complement and interact with NE which is known to have central and peripheral effects on resting metabolic rate (RMR), food intake and body weight of rats. We have studied the effect of chronic peripheral administration of NPY on the metabolic action of NE in obese adult male rats. A group of 20 adult male obese (fa/fa) Zucker rats were acclimated to environmental temperature of either 28 degrees C or 17 degrees C. Each group was divided into 5 subgroups: (I) untreated controls; (II) Carrier-treated Controls; (III) NPY treated; (IV) NE treated and (V) NPY + NE treated. In subgroups II-V, Alzet (2002) osmotic minipumps were implanted under the skin in the interscapular region. Pumps were filled with carrier alone (subgroups II) plus NPY (subgroups III), or NE (subgroups IV), or both (subgroups V). Delivery rates were calculated to be 0.5 microgram/h NPY; 20 micrograms/h NE, extending over a period of 14 days. Starting from day 2, cumulative food intake and cumulative changes in total body weight were measured every two days. RMR of the animals was measured on days 2, 8, and 14 (indirectly as minimal oxygen consumption). On day 15 animals were sacrificed and specimens of the interscapular BAT were fixed for microscopic examination and measurement of the cross-sectional area of the triglyceride droplets as index for tissue activity. In warm environmental conditions the combined treatment with NE and NPY was the only treatment that caused significant reduction of total body weight by inhibiting food intake and enhancing RMR. The involvement of BAT in this function was observed. In the cold environment the NE and NPY together showed similar but less enhancing effect on body weight; this was mainly due to the significant depression of food intake and slight metabolic response. BAT of this group showed significant response to the combined treatment and slight response to the separate treatments with either NE or NPY.