8369 Overexpression of Neurosecretory Protein GL, a Novel Small Secretory Protein, Induces Fat Accumulation in Mice

Abstract Disclosure: K. Ukena: None. Y. Narimatsu: None. A. Ogasawara: None. M. Furumitsu: None. E. Iwakoshi-Ukena: None. Hypothalamic neuropeptides and peripheral factors influence food intake, body mass, and energy expenditure. For instance, neuropeptide Y (NPY)/agouti-related peptide (AgRP) are potent orexigenic factors and α-melanocyte-stimulating hormone (α-MSH) is an anorexigenic factor, respectively. In addition, leptin and insulin derived from peripheral tissues act on the hypothalamus to influence energy homeostasis. Precise hypothalamic control of energy balance affects puberty, thermoregulation, energy storage, and survival during different life-history stages. We have previously discovered a novel cDNA encoding the precursor of a neurosecretory small protein in the hypothalamus of birds and rodents (1, 2). The precursor protein contained a signal peptide sequence, a mature peptide sequence with 80 amino acid residues, a glycine amidation signal, and a dibasic amino acid cleavage site. Because the predicted C-terminal amino acids of the peptide were Gly-Leu-NH2, the small protein was named neurosecretory protein GL (NPGL). Quantitative RT-PCR analysis demonstrated that NPGL mRNA was expressed exclusively in the mediobasal hypothalamus (MBH), including the arcuate nucleus, and the expression was elevated on food deprivation in rodents. This finding led us to predict that NPGL was involved in the regulation of energy homeostasis. Indeed, using NPGL administration and neutralizing antibody administration in rats, we established that NPGL increased lipid accumulation in white adipose tissue (3). In the present study, to investigate the physiological function of NPGL in mice, we induced its overexpression using an adeno-associated virus (AAV) vector in NPGL-Cre driver mice. We then monitored food intake and recorded body mass changes. Npgl overexpression increased body mass. We also found that the overexpression resulted in increased masses of white adipose tissue and interscapular brown adipose tissue. Taken together, these results provide evidence for NPGL as a novel regulator of fat deposition in adipose tissues. Reference: (1) Ukena et al., Biochem. Biophys. Res. Commun. 2014 446:298-303. (2) Ukena, Gen. Comp. Endocrinol. 2018 260:164-170. (3) Iwakoshi-Ukena et al., eLife 2017 6:e28527. Presentation: 6/3/2024