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

作　　者：刘晓璇 张晗思 韩晓静 尚晓迪 康静 林俊堂 闫欣[1,2] 乔梁 LIU Xiao-xuan;ZHANG Han-si;HAN Xiao-jing;SHANG Xiao-di;KANG Jing;LIN Jun-tang;YAN Xin;QIAO Liang(National Joint Engineering Laboratory of Stem Cells and Biotherapy,School of Life Science and Technology,Xinxiang Medical University,He’nan Xinxiang 453003,China;He’nan Key Laboratory of Medical Tissue Regeneration,Xinxiang Medical University,He’nan Xinxiang 453003,China;School of Medical Engineering,Xinxiang Medical University,He’nan Xinxiang 453003,China)

机构地区：[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 [2]河南省医用组织再生重点实验室,河南新乡453003 [3]新乡医学院医学工程学院,河南新乡453003

出　　处：《解剖学报》2024年第4期452-459,共8页Acta Anatomica Sinica

基　　金：国家自然科学基金(82071326,81870587);河南省重点研发与推广专项(科技攻关)(222102310086,232102310288);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,XYBSKYZZ202124)。

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。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 

分 类 号：R589[医药卫生—内分泌]