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

Abstract

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.

Neurosecretory Protein GM–Expressing Neurons Participate in Lipid Storage and Inflammation in Newly Developed Cre Driver Male Mice

“…AAV-based vectors were prepared following previous reports [23,29,30] using pAAV-hSyn-DIO-Npgm-P2A-eGFP, pAAV-hSyn-DIO-hM3Dq-mCherry, pAAV-EF1α-DIO-mCherry (#50462, addgene), and pAAV-flex-taCasp3-TEVp (#45580, addgene). The AAV-based vectors were stored at −80 • C until use.…”

“…AAV injection was performed as described in previous methods [23,29,30]. NPGM-Cre mice were anesthetized using isoflurane.…”

The Role of Hypothalamic Neuropeptides in Regulation of Liver Functions in Health and Disease

“…More recently, the same research group investigated the effects of NPLG on obesity using mice that overexpressed the NPGL gene in the hypothalamus and concluded that NPGL peptide in excess could act as an obesogenic factor within a short period (e.g., 8 weeks in mice) causing accumulation of lipids in both adipose and liver [34]. Moreover, a study on sugar consumption in relation to obesity and liver steatosis concluded that mice overexpressing hypothalamic NPGL, and fed a medium fat diet supplemented with either glucose or fructose, resulted in increased body weight and fatty liver with the fructose-rich diet but not with a diet rich in glucose [35]. These data emphasize the specific and very different effects of fructose versus glucose on NPGL-induced signaling in the liver and warrant further research on the effects of specific nutrients on neuropeptides and their signaling in relation to metabolism.…”

Nanomolar range of FAM237B can activate receptor GPR83

“…The copyright holder for this preprint (which this version posted May 5, 2023. ; https://doi.org/10.1101/2023.05.04.539513 doi: bioRxiv preprint Matsuura et al 2017;Narimatsu et al 2021Narimatsu et al , 2022aNarimatsu et al , 2022bNarimatsu et al , 2022cShikano et al 2018aShikano et al , 2019Shikano et al , 2020. Administration or overexpression of FAM237A in murine or avian models typically increased food intake and fat accumulation, suggesting this neuropeptide is implicated in the regulation of energy metabolism.…”