Neurosecretory protein GL stimulates food intake, de novo lipogenesis, and onset of obesity.

Eiko Iwakoshi-Ukena,Yuta Ochi,Megumi Furumitsu,Kazuyoshi Ukena,Shusuke Taniuchi,George E Bentley,Yasuhiko Minokoshi,Shiki Okamoto,Tsutomu Sasaki,Kenshiro Shikano,Lance J Kriegsfeld,Kunihiro Kondo

doi:10.7554/elife.28527

Abstract

Mechanisms underlying the central regulation of food intake and fat accumulation are not fully understood. We found that neurosecretory protein GL (NPGL), a newly-identified neuropeptide, increased food intake and white adipose tissue (WAT) in rats. NPGL-precursor gene overexpression in the hypothalamus caused increases in food intake, WAT, body mass, and circulating insulin when fed a high calorie diet. Intracerebroventricular administration of NPGL induced de novo lipogenesis in WAT, increased insulin, and it selectively induced carbohydrate intake. Neutralizing antibody administration decreased the size of lipid droplets in WAT. Npgl mRNA expression was upregulated by fasting and low insulin levels. Additionally, NPGL-producing cells were responsive to insulin. These results point to NPGL as a novel neuronal regulator that drives food intake and fat deposition through de novo lipogenesis and acts to maintain steady-state fat level in concert with insulin. Dysregulation of NPGL may be a root cause of obesity.

Highlights

Dysregulated energy balance can result in obesity and lead to serious health problems such as diabetes and cardiovascular disease (Steinberger and Daniels, 2003; Hill et al, 2012; Ahima and Lazar, 2013)
Histological analyses showed that both NPGL-precursor gene (Npgl) mRNA and its mature protein were localized to the lateroposterior division of the arcuate nucleus (Arc) (ArcLP) and the ventral tuberomammillary nucleus (VTM) (Figure 1D–I)
We found that mRNA expression levels of Acc, Fas, Adpn, and Atgl in retroperitoneal WAT (rWAT) significantly increased after Npgl overexpression, but no differences were detected in liver (Figure 3E)

Summary

Introduction

Dysregulated energy balance can result in obesity and lead to serious health problems such as diabetes and cardiovascular disease (Steinberger and Daniels, 2003; Hill et al, 2012; Ahima and Lazar, 2013). It is important for human health to gain insight into the physiological mechanisms underlying the regulation of obesity. As obesity results mainly from overfeeding, most research to date has focused on hypothalamic regulation of feeding and satiety. Several hypothalamic neuropeptides and peripheral factors influence food intake and body mass (Schwartz and Porte, 2005; Morton et al, 2006, 2014). The arcuate nucleus (Arc) of the Iwakoshi-Ukena et al eLife 2017;6:e28527.

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