首页|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

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

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

ObesityLeptinHypothalamusAdipose tissueImmunofluorescenceReal-time PCRLeptin-deficient obese mouse

刘晓璇、张晗思、韩晓静、尚晓迪、康静、林俊堂、闫欣、乔梁

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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

新乡医学院医学工程学院,河南新乡 453003

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

国家自然科学基金国家自然科学基金河南省重点研发与推广专项(科技攻关)河南省重点研发与推广专项(科技攻关)河南省高等学校青年骨干教师培养计划新乡医学院人才(博士)支持计划新乡医学院人才(博士)支持计划

82071326818705872221023100862321023102882020GGJS148505511XYBSKYZZ202124

2024

10.16098/j.issn.0529-1356.2024.04.011

解剖学报
中国解剖学会

解剖学报

CSTPCD
影响因子：0.462
ISSN：0529-1356
年,卷(期)：2024.55(4)