We recently identified a cDNA encoding a novel small secretory protein in the hypothalamus of birds and rodents. This precursor protein consisted of a signal peptide sequence, a putative small protein sequence, a glycine amidation signal, and dibasic amino acids, which are cleaved by a prohormone convertase. It was given the name neurosecretory protein GL (NPGL). In the rat, NPGL-producing neurons are localized to the lateroposterior portion of the arcuate nucleus (ArcLP) and the ventral tuberomammillary nucleus (VTM). These structures are involved in the regulation of feeding behavior and energy homeostasis. The expression of NPGL mRNA in the mediobasal hypothalamus (MBH), including the ArcLP and VTM, was altered in fasted rats, insulin-administered rats, and genetically obese (fa/fa) Zucker rats. We therefore concluded that NPGL might modulate energy homeostasis.

In order to investigate the biological action of NPGL, we chronically injected NPGL into the cerebral ventricle of male rats for 2 weeks, using an osmotic pump. We then supplied the rats with either a control or a high calorie diet, and measured their body temperature, body weight, and food intake. In the control diet group, the infusion of NPGL decreased body temperature and suppressed weight gain, without affecting food intake. However, the ratio of white adipose tissue (WAT) to body weight was significantly increased. In contrast, the injection of NPGL into the high calorie diet group led to increased food intake but no gain in body weight. The ratio of WAT to body weight also increased in this group. In conclusion, the results suggest that chronic central infusion of NPGL in rats may suppress energy consumption and growth, and accelerate fat gain. Furthermore, NPGL might result in a preference for a high calorie diet.