畜牧兽医学报 ›› 2024, Vol. 55 ›› Issue (7): 3185-3192.doi: 10.11843/j.issn.0366-6964.2024.07.036

• 基础兽医 • 上一篇    下一篇

胰淀素作用于背外侧被盖核胆碱乙酰转移酶神经元调节小鼠体重

曹晓娟1(), 刘昊东2,3, 李鹏辉2,3, 李嘉成2,3, 樊奇2,3, 王星2,3, 李彩琴2,3, 杨子程2,3, 郭永清1, 陈玉洁1, 张小宇1, 海日汗1, 杜晨光1,2,3,*()   

  1. 1. 内蒙古农业大学职业技术学院, 包头 014109
    2. 内蒙古自治区基础兽医学重点实验室, 呼和浩特 010018
    3. 内蒙古农业大学兽医学院, 呼和浩特 010018
  • 收稿日期:2022-11-08 出版日期:2024-07-23 发布日期:2024-07-24
  • 通讯作者: 杜晨光 E-mail:zykyk@163.com;duc@imau.edu.cn
  • 作者简介:曹晓娟(1979-),女,山西太谷人,硕士,主要从事动物营养与饲料研究,E-mail: zykyk@163.com
  • 基金资助:
    国家自然科学基金(32060204);内蒙古科技攻关计划(2021GG0199);内蒙古自然科学基金(2020MS03035);内蒙古自治区教育厅高等学校科学研究项目(NJZY22535);内蒙古自治区直属高校基本科研业务费项目(BR220150);内蒙古自治区高等学校科学研究重点项目(NJZZ22529);内蒙古自治区教育厅高等学校科学研究项目(NJZY23120)

Amylin Acts on Choline Acetyltransferase Neurons in the Lateral Dorsal Tegmental Nucleus (LDT) to Regulate Body Weight of Mice

Xiaojuan CAO1(), Haodong LIU2,3, Penghui LI2,3, Jiacheng LI2,3, Qi FAN2,3, Xing WANG2,3, Caiqin LI2,3, Zicheng YANG2,3, Yongqing GUO1, Yujie CHEN1, Xiaoyu ZHANG1, Rihan HAI1, Chenguang DU1,2,3,*()   

  1. 1. Vocational and Technical College of Inner Mongolia Agricultural University, Baotou 014109, China
    2. Key Laboratory of Basic Veterinary Medicine of Inner Mongolia Autonomous Region, Hohhot 010018, China
    3. College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China
  • Received:2022-11-08 Online:2024-07-23 Published:2024-07-24
  • Contact: Chenguang DU E-mail:zykyk@163.com;duc@imau.edu.cn

摘要:

胰淀素(amylin)作用于背外侧被盖核(lateral dorsal tegmental nucleus,LDT),诱导减肥和抑食效应,并激活背肩胛棕色脂肪组织(interscapular brown adipose tissue, IBAT)产热。多种食欲激素受体与胆碱乙酰转移酶(choline acetyltransferase, ChAT)神经元共同定位于LDT中,以调节饱腹感和能量消耗。然而,LDT的ChAT神经元是否参与胰淀素介导的体重调节作用尚待探索。作者拟通过免疫荧光检测小鼠LDT中原癌基因蛋白(c-Fos)和ChAT神经元的表达,逆行示踪技术确认LDT的下游神经核团,神经元损伤试验分析胰淀素作用的神经机制。结果显示:腹腔注射胰淀素显著降低小鼠体重,并显著促进LDT和臂旁核(PBN)中c-Fos和ChAT神经元表达。ChAT和神经型一氧化氮合成酶(nNOS)神经元在LDT、PBN和迷走神经背侧核(DMV)中共表达。逆行示踪试验证明LDT向PBN神经元发送神经投射。此外,损伤LDT和PBN神经元可降低胰淀素的减肥效果。LDT是连接PBN的能量平衡调节中枢,ChAT神经元参与介导胰淀素的体重调节过程。

关键词: 肥胖, 胆碱乙酰转移酶, 胰淀素, 下丘脑, 背外侧被盖核

Abstract:

Amylin acts on the lateral dorsal tegmental nucleus (LDT), induces weight loss and diet-suppressive effects, and activates dorsal scapular brown adipose tissue (IBAT) to produce heat. Multiple appetite hormone receptors colocalized with choline acetyltransferase (ChAT) neurons in LDT to modulate saturation and energy expenditure. However, it remains to be determined whether ChAT neurons in LDT are involved in amylin-mediated weight regulation. Immunofluorescence was conducted to detect the expression of c-Fos and ChAT neurons in mouse LDT, retrograde tracer analysis was selected to confirme the downstream nucleus mass of LDT, and neuronal damage assays was conducted to analyze the neuromechanism of amylin action. Results showed that intraperitoneal administration of amylin significantly reduced the body weight of mice and significantly increased the expression of c-Fos and ChAT neurons in both the LDT and parabrachial nucleus (PBN). ChAT and neuronal nitric oxide synthase (nNOS) neurons were co-expressed in the dorsal motor nucleus of the vagus (DMV). Retrograde tracer experiments demonstrated that LDTs send nerve projections to PBN neurons. Furthermore, injury of LDT and PBN neurons reduced the weight loss of amylin. LDT is the center of energy balance regulation connected to PBN, and the ChAT neurons of this circuit are involved in the process of weight regulation of amylin.

Key words: obesity, choline acetyltransferase, amylin, hypothalamus, lateral dorsal tegmental nucleus

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