解剖学报2024,Vol.55Issue(4) :452-459.DOI:10.16098/j.issn.0529-1356.2024.04.011

瘦素对肥胖小鼠下丘脑神经元活性及脂肪组织代谢的影响

Effects of leptin on hypothalamic neuronal activity and adipose tissue metabolism in obese mice

刘晓璇 张晗思 韩晓静 尚晓迪 康静 林俊堂 闫欣 乔梁
解剖学报2024,Vol.55Issue(4) :452-459.DOI:10.16098/j.issn.0529-1356.2024.04.011

瘦素对肥胖小鼠下丘脑神经元活性及脂肪组织代谢的影响

Effects of leptin on hypothalamic neuronal activity and adipose tissue metabolism in obese mice

刘晓璇 1张晗思 1韩晓静 1尚晓迪 1康静 2林俊堂 3闫欣 1乔梁1
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作者信息

  • 1. 河南省干细胞与生物治疗工程研究中心,新乡医学院生命科学技术学院,河南新乡 453003;河南省医用组织再生重点实验室,河南新乡 453003
  • 2. 河南省干细胞与生物治疗工程研究中心,新乡医学院生命科学技术学院,河南新乡 453003
  • 3. 河南省干细胞与生物治疗工程研究中心,新乡医学院生命科学技术学院,河南新乡 453003;新乡医学院医学工程学院,河南新乡 453003
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摘要

目的 探讨瘦素对肥胖小鼠下丘脑神经元活性的影响,以及对脂肪组织脂质代谢的作用.方法 选取10只瘦素基因纯合突变(ob/ob)小鼠和同窝出生的10只野生型(WT)小鼠作为研究对象,随机分为对照组和瘦素治疗组.通过免疫荧光染色、HE染色和Real-time PCR分析小鼠阿黑皮质素原(POMC)神经元和酪氨酸羟化酶(TH)神经元活性、脂肪组织形态变化及脂质相关基因的表达.结果 与WT小鼠相比,ob/ob小鼠POMC神经元和TH+神经元活性显著降低,脂肪组织和肝脏组织细胞直径明显增大,皮下白色脂肪中产热相关基因解耦联蛋白1(UCP1)、细胞色素C氧化酶亚基8b(Cox8b)和细胞死亡激活剂CIDE-A(Cidea)的表达显著降低,脂质合成相关基因固醇调节元件结合蛋白1(Srebp1)和脂肪酸合酶(Fas)的表达显著升高;瘦素治疗后,WT和ob/ob小鼠POMC神经元和TH+神经元活性增加,ob/ob小鼠脂肪组织和肝脏组织细胞直径明显减小,空泡变性程度降低,褐色脂肪组织产热相关基因和脂解相关基因的表达显著升高,脂质合成相关基因的表达显著降低.结论 瘦素通过激活ob/ob小鼠下丘脑POMC神经元和外周脂肪组织交感神经系统,抑制食物摄入,增加脂肪降解并降低脂质合成作用,从而改善脂肪白色化并抑制肥胖的发展.

Abstract

Objective To investigate the effects of leptin on hypothalamic neuron activity and lipid metabolism in adipose tissue of obese mice.Methods 10 leptin-deficient obese(ob/ob)mice with homozygous mutation of leptin gene and 10 wild-type(WT)mice born in the same litter were randomly divided into control group and leptin treatment group.The activity of pro-opiomelanocortin(POMC)neurons and tyrosine hydroxylase(TH+)neurons,the morphological changes of adipose tissue and the expression of lipid-related genes were analyzed by immunofluorescent staining,HE staining and Real-time PCR.Results Compared with the WT mice,the ob/ob mice showed decreased activity of POMC neurons and TH+neurons and larger cell diameter in adipose tissue and liver tissue.In addition,the expressions of heat-related genes uncoupling protein 1(UCP1),cytochrome c oxidase subunit 8B(Cox8b)and cell death-inducing DNA fragmentation factor,alpha subunit-like effector A(Cidea)in subcutaneous white fat in ob/ob mice decreased significantly,and the expressions of lipid synthesis-related genes sterol regulatory element binding transcription factor 1(Srebp1)and fatty acid synthase(Fas)increased significantly.After treated with leptin,the activities of POMC and TH+neurons were increased,and the cellular diameter and the degree of vacuolar degeneration were reduced in the adipose tissue and liver.Further analyses showed that the expressions of thermogenesis-related genes and lipolysis-related genes were increased,but expressions of lipid synthesis-related genes were reduced in brown adipose tissue.Conclusion Leptin treatment could prevent the increasing of obesity in ob/ob mice,which is associated with increased lipolysis and reduced lipid synthesis through activation of hypothalamic POMC neurons and peripheral adipose tissue sympathetic nervous system.

关键词

肥胖/瘦素/下丘脑/脂肪组织/免疫荧光/实时定量聚合酶链反应/瘦素基因纯合突变小鼠

Key words

Obesity/Leptin/Hypothalamus/Adipose tissue/Immunofluorescence/Real-time PCR/Leptin-deficient obese mouse

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基金项目

国家自然科学基金(82071326)

国家自然科学基金(81870587)

河南省重点研发与推广专项(科技攻关)(222102310086)

河南省重点研发与推广专项(科技攻关)(232102310288)

河南省高等学校青年骨干教师培养计划(2020GGJS148)

新乡医学院人才(博士)支持计划(505511)

新乡医学院人才(博士)支持计划(XYBSKYZZ202124)

出版年

2024
解剖学报
中国解剖学会

解剖学报

CSTPCD
影响因子:0.462
ISSN:0529-1356
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