Hypothalamic Overexpression of Neurosecretory Protein GL Leads to Obesity in Male C57BL/6J Mice

Narimatsu, Yuki; Ukena, Kazuyoshi; Fukumura, Kazuya; Shikano, Kenshiro; Furumitsu, Megumi; Morishita, Masahiro; Bentley, G.; Kriegsfeld, Lance J.; Ukena, Kazuyoshi

doi:10.1159/000518969

Cited by 14 publications

(27 citation statements)

References 41 publications

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“…Sugar is the root cause of many diseases, such as metabolic syndrome, via dysfunction of systemic energy metabolism. We recently showed that hypothalamic overexpression of Npgl, a novel precursor gene encoding a small protein, induces obesity by enhancing the palatability of carbohydrates in rodents [15,20]. However, the difference in lipogenic efficiency of NPGL with different types of sugars remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, NPGL promoted the intake of carbohydrate and fat accumulation via de novo lipogenesis in rats [15,19]. Moreover, overexpression of the NPGL-precursor gene (Npgl) rapidly induced obesity in mice [20]. Thus, we speculate that NPGL exerts obesogenic effects by evoking the palatability of sugars in birds and mammals.…”

Section: Introductionmentioning

confidence: 90%

“…One-way ANOVA showed that body mass was increased by Npgl overexpression in mice fed the two diets (Figure 1D). We subsequently calculated food efficiency, which is an index of the amount of mass gained per unit of food intake [20]. Two-way ANOVA with repeated measures revealed the main effects of time and treatment on food efficiency (Figure 1E).…”

Section: Effects Of Npgl-precursor Gene Overexpression On Food Intake...mentioning

confidence: 99%

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Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet

Narimatsu

Naito

Moriwaki

et al. 2022

IJMS

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Sugar consumption can readily lead to obesity and metabolic diseases such as liver steatosis. We previously demonstrated that a novel hypothalamic neuropeptide, neurosecretory protein GL (NPGL), promotes fat accumulation due to the ingestion of sugar by rats. However, differences in lipogenic efficiency of sugar types by NPGL remain unclear. The present study aimed to elucidate the obesogenic effects of NPGL on mice fed different sugars (i.e., sucrose or fructose). We overexpressed the NPGL-precursor gene (Npgl) in the hypothalamus of mice fed a medium-fat/medium-sucrose diet (MFSD) or a medium-fat/medium-fructose diet (MFFD). Food intake and body mass were measured for 28 days. Body composition and mRNA expression of lipid metabolic factors were measured at the endpoint. Npgl overexpression potently increased body mass with fat accumulation in the white adipose tissue of mice fed MFFD, although it did not markedly affect food intake. In contrast, we observed profound fat deposition in the livers of mice fed MFFD but not MFSD. In the liver, the mRNA expression of glucose and lipid metabolic factors was affected in mice fed MFFD. Hence, NPGL induced liver steatosis in mice fed a fructose-rich diet.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Section: Effects Of Npgl-precursor Gene Overexpression On Food Intake...mentioning

confidence: 99%

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Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet

Narimatsu

Naito

Moriwaki

et al. 2022

IJMS

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“…Our previous studies have indicated that NPGL participates in energy homeostasis, including feeding behavior and fat accumulation in rodents [ 28 , 29 , 30 , 31 ]. In addition, we found that NPGL cell bodies are localized in the ArcLP, and NPGL-containing fibers project to several anterior hypothalamic regions in mice [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Npgl mRNA expression is increased by fasting in mice, whereas it is reduced by a high-fat diet [ 29 ]. In addition, the administration of NPGL and Npgl overexpression in the hypothalamus increases food intake and fat accumulation in rats and mice [ 28 , 30 , 31 ]. These data suggest that NPGL is involved in the energy metabolism of rodents.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Analysis of Neurotransmitters in Neurosecretory Protein GL-Producing Neurons of the Mouse Hypothalamus

et al. 2022

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We recently discovered a novel neuropeptide of 80 amino acid residues: neurosecretory protein GL (NPGL), in the hypothalamus of birds and rodents. NPGL is localized in the lateral posterior part of the arcuate nucleus (ArcLP), and it enhances feeding behavior and fat accumulation in mice. Various neurotransmitters, such as catecholamine, glutamate, and γ-aminobutyric acid (GABA), produced in the hypothalamus are also involved in energy metabolism. The colocalization of neurotransmitters and NPGL in neurons of the ArcLP leads to the elucidation of the regulatory mechanism of NPGL neurons. In this study, we performed double immunofluorescence staining to elucidate the relationship between NPGL and neurotransmitters in mice. The present study revealed that NPGL neurons did not co-express tyrosine hydroxylase as a marker of catecholaminergic neurons and vesicular glutamate transporter-2 as a marker of glutamatergic neurons. In contrast, NPGL neurons co-produced glutamate decarboxylase 67, a marker for GABAergic neurons. In addition, approximately 50% of NPGL neurons were identical to GABAergic neurons. These results suggest that some functions of NPGL neurons may be related to those of GABA. This study provides insights into the neural network of NPGL neurons that regulate energy homeostasis, including feeding behavior and fat accumulation.

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Nanomolar range of FAM237B can activate receptor GPR83

Li,

Wang,

et al. 2023

Amino Acids

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The orphan G protein-coupled receptor 83 (GPR83) is implicated in the regulation of energy metabolism and certain anxiety-related behaviors. Our recent study confirmed that family with sequence similarity 237 member A (FAM237A), also known as neurosecretory protein GL (NPGL), is an efficient agonist for GPR83, but did not support the proprotein convertase subtilisin/kexin type 1 inhibitor (PCSK1N, also known as proSAAS)-derived peptide PEN and the procholecystokinin-derived peptide proCCK56-63 as ligands of this receptor. FAM237B (also known as NPGM) is a paralog of FAM237A that was previously reported as a weak agonist for GPR83 with approximately 100-fold lower activity in an inositol 1-phosphate accumulation assay.In the present study, we prepared mature human FAM237B via an intein-fusion approach and measured its activity towards human GPR83 via a NanoLuc Binary Technology (NanoBiT)-based ligand receptor binding assay and a NanoBiT-based β-arrestin recruitment assay. Mature FAM237B displayed moderately lower activity than its paralog FAM237A in these binding and activation assays, but could cause a significant activation effect at the nanomolar range (1 10 nM). Thus, FAM237B appears to be another endogenous agonist for receptor GPR83.

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Hypothalamic Overexpression of Neurosecretory Protein GL Leads to Obesity in Male C57BL/6J Mice

Cited by 14 publications

References 41 publications

Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet

Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet

Immunohistochemical Analysis of Neurotransmitters in Neurosecretory Protein GL-Producing Neurons of the Mouse Hypothalamus

Nanomolar range of FAM237B can activate receptor GPR83

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