Hypothalamic Overexpression of Neurosecretory Protein GL Leads to Obesity in Male C57BL/6J Mice
Hypothalamic Overexpression of Neurosecretory Protein GL Leads to Obesity in Male C57BL/6J Mice
复制标题
DOI：
10.1159/000518969
复制
发表时间：
2021-08-12
影响因子：
4.1
通讯作者：
Ukena, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Narimatsu, Yuki;Iwakoshi-Ukena, Eiko;Ukena, Kazuyoshi
简介肥胖的机制尚不完全清楚，因此需要创建新的动物模型来研究代谢紊乱。我们之前发现神经分泌蛋白GL（NPGL）是一种新发现的下丘脑神经肽，与大鼠的进食行为和脂肪积累有关。然而，在任何动物模型中，NPGL 对肥胖的影响仍不清楚。本研究试图阐明 NPGL 是否会导致肥胖倾向小鼠品系 C57BL/6J 的肥胖。方法我们使用腺相关病毒在正常饲料 (NC) 或高热量饮食 (HCD) 喂养的雄性 C57BL/6J 小鼠的下丘脑中过表达 NPGL 前体基因 (Npgl)。 Npgl 过度表达 9 周后，除了食物摄入量和体重之外，我们还测量了脂肪组织、肌肉和几个器官的质量。为了评估 Npgl 过表达对外周组织的影响，我们通过定量 RT-PCR 分析了脂质代谢相关基因的 mRNA 表达。在体重明显增加之前，使用 O 2/CO 2 代谢测量来评估全身能量消耗。结果在 NC 和 HCD 下，Npgl 过度表达增加了食物摄入量、体重、脂肪组织和肝脏质量以及食物效率，导致 8 周内可观察到肥胖。此外，我们观察到脂肪组织和肝脏中的脂肪积累。此外，Npgl 过表达后，白色脂肪组织和肝脏中脂质代谢相关因子的 mRNA 表达增加。 NPGL过表达抑制了黑暗时期的能量消耗。结论综上所述，本研究表明NPGL可以作为一种在小鼠体内短时间内起作用的致肥因子。因此，这种Npgl过表达诱导的肥胖可以广泛应用于从基因到行为的肥胖病因学研究。
IntroductionThe mechanisms underlying obesity are not fully understood, necessitating the creation of novel animal models for the investigation of metabolic disorders. We have previously found that neurosecretory protein GL (NPGL), a newly identified hypothalamic neuropeptide, is involved in feeding behavior and fat accumulation in rats. However, the impact of NPGL on obesity remains unclear in any animal model. The present investigation sought to elucidate whether NPGL causes obesity in the obesity-prone mouse strain C57BL/6J.MethodsWe overexpressed the NPGL-precursor gene (Npgl) in the hypothalamus using adeno-associated virus in male C57BL/6J mice fed normal chow (NC) or a high-calorie diet (HCD). After 9 weeks of Npgl overexpression, we measured adipose tissues, muscle, and several organ masses in addition to food intake and body mass. To assess the effects of Npgl overexpression on peripheral tissues, we analyzed mRNA expression of lipid metabolism-related genes by quantitative RT-PCR. Whole body energy consumption was assessed using an O 2/CO 2 metabolism measurement before an apparent increase in body mass.ResultsNpgl overexpression increased food intake, body mass, adipose tissues and liver masses, and food efficiency under both NC and HCD, resulting in obesity observable within 8 weeks. Furthermore, we observed fat accumulation in adipose tissues and liver. Additionally, mRNA expression of lipid metabolism-related factors was increased in white adipose tissue and the liver after Npgl overexpression. Npgl overexpression inhibited energy expenditure during a dark period.ConclusionTaken together, the present study suggests that NPGL can act as an obesogenic factor that acts within a short period of time in mice. As a result, this Npgl overexpression-induced obesity can be widely applied to study the etiology of obesity from genes to behavior.