Overexpression of the Gene Encoding Neurosecretory Protein GL Precursor Prevents Excessive Fat Accumulation in the Adipose Tissue of Mice Fed a Long-Term High-Fat Diet.

Keisuke Fukumura,Yuki Narimatsu,Megumi Furumitsu,Kazuyoshi Ukena,Eiko Iwakoshi-Ukena,Shogo Moriwaki

doi:10.3390/molecules26196006

Keisuke Fukumura, Yuki Narimatsu + Show 4 more

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https://doi.org/10.3390/molecules26196006

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Journal: Molecules (Basel, Switzerland)	Publication Date: Oct 3, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: Hiroshima University

Abstract

We previously identified a novel small hypothalamic protein, neurosecretory protein GL (NPGL), which induces feeding behavior and fat accumulation in rodents depending on their diet. In the present study, we explored the effects of NPGL on feeding behavior and energy metabolism in mice placed on a long-term high-fat diet with 60% calories from fat (HFD 60). Overexpression of the NPGL precursor gene (Npgl) over 18 weeks increased food intake and weight. The weekly weight gain of Npgl-overexpressing mice was higher than that of controls until 7 weeks from induction of overexpression, after which it ceased to be so. Oral glucose tolerance tests showed that Npgl overexpression maintained glucose tolerance and increased blood insulin levels, and intraperitoneal insulin tolerance tests showed that it maintained insulin sensitivity. At the experimental endpoint, Npgl overexpression was associated with increased mass of the perirenal white adipose tissue (WAT) and decreased mass of the epididymal WAT (eWAT), resulting in little effect on the total WAT mass. These results suggest that under long-term HFD 60 feeding, Npgl overexpression may play a role in avoiding metabolic disturbance both by accelerating energy storage and by suppressing excess fat accumulation in certain tissues, such as the eWAT.

Highlights

Published: 3 October 2021Obesity has become a public health problem of global scale
We have shown that overexpression of the neurosecretory protein GL (NPGL) precursor gene (Npgl) elicits food intake and subsequent fat accumulation in the white adipose tissue (WAT) of rats through de novo lipogenesis using dietary carbohydrates [23]
We performed stereotaxic surgery to induce Npgl overexpression in the mediobasal hypothalamus (MBH) of high-fat diet with 60% calories from fat (HFD 60)-fed mice using an adeno-associated virus (AAV) vector, conducted a series of experiments to explore the effects of Npgl overexpression on feeding behavior, metabolism, glucose tolerance, and insulin sensitivity (Figure 1A)

Summary

Introduction

Obesity has become a public health problem of global scale. Treatment of this increasingly prevalent disease presents a vast economic burden, and there are no definitive therapeutic approaches. Excess fat accumulation induces chronic inflammation in adipose tissue, leading to systemic insulin resistance and glucose intolerance [4,5]. Several neuropeptides regulating feeding behavior and metabolism have been discovered in the arcuate nucleus of the hypothalamus, including potent orexigenic and anorexigenic factors such as neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC)-derived α-melanocyte-stimulating hormone [6,7,8]. Some studies have reported that some of these neuropeptides, such as NPY, play a crucial role in feeding behavior and in the regulation of systemic insulin sensitivity [9]. Peripheral factors in regulation of feeding include ghrelin and Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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