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外侧臂旁核中的胃饥饿素会影响葡萄糖感应神经元的兴奋性,增加食物摄入量和体重。

Ghrelin in the lateral parabrachial nucleus influences the excitability of glucosensing neurons, increases food intake and body weight.

作者信息

Zhang Caishun, Yuan Junhua, Lin Qian, Li Manwen, Wang Liuxin, Wang Rui, Chen Xi, Jiang Zhengyao, Zhu Kun, Chang Xiaoli, Wang Bin, Dong Jing

机构信息

Special Medicine Department, College of Basic Medicine, Qingdao University, Qingdao, China.

Hyperbaric Oxygen Therapy Department, Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China.

出版信息

Endocr Connect. 2020 Dec;9(12):1168-1177. doi: 10.1530/EC-20-0285.

Abstract

Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR-/- mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose-sensitive neurons to explore potential udnderlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 h, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR-/- mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GE and GI neurons.

摘要

胃饥饿素在食物摄入、体重和能量代谢的调节中起关键作用。然而,胃饥饿素在外侧臂旁核(LPBN)中的这些作用尚未得到研究。将C57BL/6J小鼠和生长激素促分泌素受体基因敲除(GHSR-/-)小鼠在右侧LPBN上方植入套管,并通过套管微量注射胃饥饿素,以研究胃饥饿素在LPBN中的作用。采用体内电生理技术记录LPBN葡萄糖敏感神经元,以探索潜在的作用机制。在LPBN中微量注射胃饥饿素在最初3小时内显著增加食物摄入量,而这种作用被[D-赖氨酸3]-生长激素释放肽-6阻断,且在GHSR-/-小鼠中消失。在LPBN中微量注射胃饥饿素还显著增加了葡萄糖兴奋(GE)神经元的放电频率,并降低了葡萄糖抑制(GI)神经元的放电频率。此外,在LPBN中微量注射胃饥饿素也显著增加了c-fos表达。在LPBN中长期注射胃饥饿素导致体重显著增加。同时,棕色脂肪组织(BAT)中解偶联蛋白1(UCP-1)的mRNA和蛋白表达水平均未观察到显著变化。这些结果表明,在C57BL/6J小鼠中,在LPBN中微量注射胃饥饿素可通过与生长激素促分泌素受体(GHSR)相互作用增加食物摄入量,长期注射也可增加体重。这些作用可能与GE和GI神经元放电频率的改变有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bac/7774750/92ecc020b317/EC-20-0285fig1.jpg

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