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

doi:10.16098/j.issn.0529-1356.2024.04.011

解剖学报 ›› 2024, Vol. 55 ›› Issue (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

刘晓璇^1,2张晗思^1,2韩晓静^1,2尚晓迪^1,2康静¹林俊堂^1,3闫欣^1,2*乔梁^1,2*

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

收稿日期:2023-06-27 修回日期:2023-08-14 出版日期:2024-08-06 发布日期:2024-08-06
通讯作者: 闫欣乔梁 E-mail:qiaoliang927@163.com
基金资助:
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

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

LIU Xiao-xuan^1,2 ZHANG Han-si^1,2 HAN Xiao-jing^1,2 SHANG Xiao-di^1,2 KANG Jing¹ LIN Jun-tang^1,3 YAN Xin^1,2* QIAO Liang^1,2*

1.National Joint Engineering Laboratory of Stem Cells and Biotherapy, School of Life Science and Technology, Xinxiang Medical University, He’nan Xinxiang 453003, China; 2.He’nan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, He’nan Xinxiang 453003, China; 3.School of Medical Engineering, Xinxiang Medical University, He’nan Xinxiang 453003, China

Received:2023-06-27 Revised:2023-08-14 Online:2024-08-06 Published:2024-08-06
Contact: YAN Xin QIAO Liang E-mail:qiaoliang927@163.com

摘要/Abstract

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。

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

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

Key words: Obesity, Leptin, Hypothalamus, Adipose tissue, Immunofluorescence, Real-time PCR, Leptin-deficient obese mouse

中图分类号:

R589.2

刘晓璇张晗思韩晓静尚晓迪康静林俊堂闫欣乔梁. 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[J]. 解剖学报, 2024, 55(4): 452-459.

LIU Xiao-xuan ZHANG Han-si HAN Xiao-jing SHANG Xiao-di KANG Jing LIN Jun-tang YAN Xin QIAO Liang. Effects of leptin on hypothalamic neuronal activity and adipose tissue metabolism in obese mice[J]. Acta Anatomica Sinica, 2024, 55(4): 452-459.

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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

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