Localization and function of neurosecretory protein GM, a novel small secretory protein, in the chicken hypothalamus

Abstract

Recently, we discovered a novel cDNA encoding the precursor of a small secretory protein, neurosecretory protein GL (NPGL), in the hypothalamic infundibulum of chickens. NPGL plays an important role in the regulation of growth and feeding. A database search indicated that the NPGL gene has a paralogous gene: neurosecretory protein GM (NPGM), also in chickens. We identified cDNA encoding the NPGM precursor in chickens. Morphological analysis showed that NPGM-containing cells are specifically localized in the medial mammillary nucleus (MM) and infundibular nucleus (IN) in the hypothalamus. In addition, we found that NPGM and NPGL are co-localized, especially in the MM. The expression levels of NPGM mRNA gradually decreased during post-hatch development, in contrast to those of NPGL mRNA. Moreover, we investigated the relationship between NPGM and other known factors. NPGM was found to be produced in histaminergic neurons in the MM. NPGM and histidine decarboxylase, a histamine-producing enzyme, displayed similar expression patterns during post-hatch development. Acute intracerebroventricular injection of NPGM decreased food intake, similar to the effect of histamine. To our knowledge, this is the first report of the localization and function of NPGM in the brain of vertebrates. These results will further advance the understanding mechanisms underlying energy homeostasis.

Effects of Overexpression of Neurosecretory Protein GL-Precursor Gene on Glucose Homeostasis and Insulin Sensitivity in Mice

“…Furthermore, homologous NPGL proteins have been discovered in mammals, including humans, rats, and mice, suggesting that the primary structure of NPGL is highly conserved in mammals and avian species [ 20 ]. In addition, its paralogous neuropeptide has been identified and named neurosecretory protein GM [ 21 ]. Similar to the effects of NPGL infusion on energy metabolism in avian species [ 22 , 23 ], acute intracerebroventricular (i.c.v.)…”

Effects of Irregular Feeding on the Daily Fluctuations in mRNA Expression of the Neurosecretory Protein GL and Neurosecretory Protein GM Genes in the Mouse Hypothalamus

“…Recently, we discovered two novel cDNAs (viz., neurosecretory protein GL ( Npgl ) and its paralog neurosecretory protein GM ( Npgm )) that encode the precursors of NPGL and NPGM, respectively, in chicken, rat, mouse, and human brains [ 29 , 30 , 31 , 32 ]. We revealed that NPGL is expressed in the mediobasal hypothalamus (MBH) of mouse and rat brains and promotes feeding and fat accumulation [ 30 , 31 , 33 ].…”

“…We revealed that NPGL is expressed in the mediobasal hypothalamus (MBH) of mouse and rat brains and promotes feeding and fat accumulation [ 30 , 31 , 33 ]. It is likely that NPGM has a similar biological function because both neurosecretory proteins are produced in the same neuron [ 32 ]. However, whether NPGL and NPGM are involved in the biological rhythm of feeding behavior and energy metabolism has not been clarified.…”

A Novel Hypothalamic Factor, Neurosecretory Protein GM, Causes Fat Deposition in Chicks

“…Recently, we discovered a novel cDNA encoding the precursor of a small secretory protein in the chick hypothalamus (Ukena et al, 2014; Shikano et al, 2018a). We named the small protein of the 83-amino acid residues as neurosecretory protein GM (NPGM) (Ukena et al, 2014; Shikano et al, 2018a). The NPGM gene is highly conserved in vertebrates, including chickens, rats, and humans (Ukena et al, 2014).…”

“…Our previous studies identified the localization of NPGM in the chick brain by in situ hybridization and immunostaining. NPGM-producing cells are localized in the infundibular nucleus (IN) and the medial mammillary nucleus (MM) of the hypothalamus in chicks (Shikano et al, 2018a). These nuclei are known to be feeding and metabolic centers in chicks.…”