We recently discovered two novel cDNAs encoding the precursor of a neurosecretory small protein in the hypothalamus of birds and rodents¹ . Both precursor proteins contained a signal peptide sequence, a mature protein sequence, a glycine amidation signal, and a dibasic amino acid cleavage site. Because the predicted C-terminal amino acids of the small proteins were Gly-Leu-NH₂ and Gly-Met-NH₂, the small proteins were named neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM), respectively. Quantitative RT-PCR analysis demonstrated that NPGL and NPGM mRNAs were expressed exclusively in the mediobasal hypothalamus (MBH), including the arcuate nucleus and the tuberomammillary nucleus, and these levels were elevated on food deprivation. This finding led us to predict that NPGL and NPGM were involved in the regulation of energy homeostasis.

To further investigate the physiological function of NPGM, we induced its overexpression in the MBH of rats using an adeno-associated virus (AAV) vector. We then monitored food intake, and recorded body weight changes. NPGM overexpression temporarily suppressed body weight gain, but it did not affect food intake. We also measured the weight of fat depot and muscles at the end of the experiment. We found that NPGM overexpression resulted in increased weight of inguinal white adipose tissue, but not interscapular brown adipose tissue that is related to thermogenesis. Furthermore, we used quantitative RT-PCR to analyze levels of a number of mRNA, including those of pituitary hormones and lipogenic enzymes. These analyses revealed that the level of growth hormone mRNA in the pituitary gland tends to be suppressed due to NPGM overexpression. In addition, the mRNA of lipogenic enzymes tends to be increased in adipose tissue, due to overexpression of NPGM. In conclusion, NPGM may play an important role in the regulation of growth and energy homeostasis.