Academic Journal
[Role of leptin receptor in the dorsal vagal complex in the inhibition of food intake in obese mice by electroacupuncture at "Zusanli" (ST36)].
| Title: | [Role of leptin receptor in the dorsal vagal complex in the inhibition of food intake in obese mice by electroacupuncture at "Zusanli" (ST36)]. |
|---|---|
| Authors: | Li K; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China.; Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029., Wang YL; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China., Xiao WH; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China., Lu LQ; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China., Lu MJ; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China., Xu TC; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China., Xu B; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China., Bao C; Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029. drbaochao@163.com., Yu Z; Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China. yuzhi@njucm.edu.cn. |
| Source: | Zhen ci yan jiu = Acupuncture research [Zhen Ci Yan Jiu] 2026 Jul 25; Vol. 51 (7), pp. 858-865. |
| Publication Type: | English Abstract; Journal Article |
| Language: | Chinese |
| Journal Info: | Publisher: Institute Of Acupuncture And Moxibustion Country of Publication: China NLM ID: 8507710 Publication Model: Print Cited Medium: Print ISSN: 1000-0607 (Print) Linking ISSN: 10000607 NLM ISO Abbreviation: Zhen Ci Yan Jiu Subsets: MEDLINE |
| Imprint Name(s): | Publication: Beijing : Institute Of Acupuncture And Moxibustion Original Publication: Beijing, China : Published and distributed by World Books, [1980- |
| MeSH Terms: | Receptors, Leptin*/metabolism , Receptors, Leptin*/genetics , Obesity*/therapy , Obesity*/metabolism , Obesity*/genetics , Obesity*/physiopathology , Vagus Nerve*/metabolism , Electroacupuncture* , Eating* , Acupuncture Points*, Leptin/metabolism ; Insulin/metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Proto-Oncogene Proteins c-fos/genetics ; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Humans ; Mice, Obese |
| Abstract: | Objectives: To observe the role of leptin receptor (LepR) in the dorsal vagal complex (DVC) in electroacupuncture(EA) -mediated regulation of food intake, so as to explore its central mechanism underlying improvement of metabolic disorders. Methods: Ten C57BLKS/JGpt mice were randomly selected as the normal group, and the remaining mice were fed with high-fat diet (HFD) to establish a obesity model. Successfully modeled mice were randomly divided into the HFD group and EA group, with 10 mice in each group. The EA group received EA stimulation (2 mA, 2 Hz /15 Hz) at bilateral "Zusanli" (ST36) for 20 min, once daily, 6 times per week, for 5 weeks. The body weight, food intake, liver tissue wet weight, inguinal white adipose tissue (iWAT) weight, epididymal white adipose tissue (eWAT) and brown adipose tissue (BAT) weight, and blood glucose levels were measured. The serum insulin and leptin contents were measured using ELISA. Immunofluorescence staining was used to detect the co-expression of LepR and proto-oncogene c-Fos protein (c-Fos), the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the nucleus tractus solitarii (NTS) and dorsal motor nucleus of the vagus nerve (DMV), and the co-expression of choline acetyltransferase (ChAT) and c-Fos in DMV. Results: Compared with the normal group, the HFD group showed a significant increase in the body weight, liver and adipose (iWAT, eWAT and BAT) wet weight, serum insulin and leptin contents, fasting blood glucose level, and glucose tolerance area under the curve (AUC, P<0.01), the number of LepR and c-Fos co-expression neurons in the DMV and NTS, p-STAT3 positive and ChAT and c-Fos co-expression neurons in the DMV were remarkably decreased (P<0.05, P<0.01). In comparison with the HFD group, the body weight, food intake, liver and adipose wet weight, serum leptin content, fasting blood glucose, and glucose tolerance AUC were significantly decreased in the EA group (P<0.01), while the number of LepR and c-Fos co-expression neurons in the DMV and NTS, p-STAT3 positive and ChAT and c-Fos co-expression neurons in the DMV were notably increased in the EA group (P<0.05, P<0.01). No significant differences were observed in the random blood glucose content and p-STAT3 positive expression in the NTS among the three groups and in the serum level of insulin after EA. Conclusions: EA at ST36 can inhibit food intake and reduce body weight in obesity mice, which may be associated with restoration of LepR-ralated signaling in the DVC and improvement of cholinergic vagal efferent neuronal activity in the DMV. |
| References: | VALENZUELA P L, CARRERA-BASTOS P, CASTILLO-GARCÍA A, et al. Obesity and the risk of cardiometabolic diseases.[J]. Nat Rev Cardiol, 2023, 20(7):475-494. PAN X F, WANG L, PAN A. Epidemiology and determinants of obesity in China[J]. Lancet Diabetes Endocrinol, 2021, 9(6):373-392. CIFUENTES L, CAMILLERI M, ACOSTA A. Gastric sensory and motor functions and energy intake in health and obesity-therapeutic implications[J]. Nutrients, 2021, 13(4):1158. OBRADOVIC M, SUDAR-MILOVANOVIC E, SOSKIC S, et al. Leptin and obesity:role and clinical implication[J]. Frontiers in Endocrinology, 2021, 12:585887. QI Y, LEE N J, IP C K, et al. Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neurons[J]. Cell Metab, 2023, 35(6):979-995. WILLIAMS D L, BASKIN D G, SCHWARTZ M W. Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin[J]. Am J Physiol Regul Integr Comp Physiol, 2009, 297(5):R1238-R1246. BRUCE K, ZHANG S Y, GARRIDO A N, et al. Pharmacological and physiological activation of TGR5 in the NTS lowers food intake by enhancing leptin-STAT3 signaling[J]. Nat Commun, 2025, 16(1):4990. ZHU F Y, LI Z M, TANG L J, et al. Progress of the mechanism research of acupuncture in treatment of diet-induced obesity(in Chinese)[J]. Acupuncture Research, 2020, 45(3):255-259. CUI L K. Establishment of obesity mouse model by long-term high fat diet(in Chinese)[J]. Journal of Jining Medical University, 2011, 34(4):240-242. GHATTA S, RAMARAO P. Increased contractile responses to 5-Hydroxytryptamine and Angiotensin II in high fat diet fed rat thoracic aorta[J]. Lipids Health Dis, 2004, 3:19. China Association of Acupuncture-Moxibustion. Nomenclature and location of acupoints commonly used in laboratory animals. Part 3:mice(in Chinese)[J]. Acupuncture Research, 2021, 46(5):445-446. CASSANO V, LEO A, TALLARICO M, et al. Metabolic and cognitive effects of ranolazine in type 2 diabetes mellitus:data from an in vivo model[J]. Nutrients, 2020, 12(2):382. MASOOD B, MOORTHY M. Causes of obesity:a review[J]. Clin Med(Lond), 2023, 23(4):284-291. JIN J, SHI Z X, HUANG Q Q, et al. Rules of acupoints selection in treating simple obesity based on date mining(in Chinese)[J]. World Science and Technology-Modernization of Traditional Chinese Medicine, 2022, 24(6):2472-2478. HUANG K P, GOODSON M L, VANG W, et al. Leptin signaling in vagal afferent neurons supports the absorption and storage of nutrients from high-fat diet[J]. Int J Obes(Lond), 2021, 45(2):348-357. PERAKAKIS N, FARR O M, MANTZOROS C S. Leptin in leanness and obesity:JACC state-of-the-art review[J]. J Am Coll Cardiol, 2021, 77(6):745-760. DE SOUZA G O, DOS SANTOS W O, DONATO J Jr. Ironing out obesity[J]. Trends Endocrinol Metab, 2024, 35(6):456-458. LIU J R, LAI F T, HOU Y J, et al. Leptin signaling and leptin resistance[J]. Med Rev, 2023(4):363-384. SCOTT M M, LACHEY J L, STERNSON S M, et al. Leptin targets in the mouse brain[J]. J Comp Neurol, 2009, 514(5):518-532. BASSI M, FURUYA W I, ZOCCAL D B, et al. Facilitation of breathing by leptin effects in the central nervous system[J]. J Physiol, 2016, 594(6):1617-1625. STEIN L M, LHAMO R, CAO A, et al. Dorsal vagal complex and hypothalamic glia differentially respond to leptin and energy balance dysregulation[J]. Transl Psychiatry, 2020, 10(1):90. NEYENS D M, BRENNER L, CALKINS R, et al. CCK-sensitive C fibers activate NTS leptin receptor-expressing neurons via NMDA receptors[J]. Am J Physiol Regul Integr Comp Physiol, 2024, 326(5):R383-R400. NEYENS D, ZHAO H, HUSTON N J, et al. Leptin sensitizes NTS neurons to vagal input by increasing postsynaptic NMDA receptor currents[J]. J Neurosci, 2020, 40(37):7054-7064. BHAGAT R, FORTNA S R, BROWNING K N. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity[J]. J Physiol, 2015, 593(1):285-303. TRAVAGLI R A, HERMANN G E, BROWNING K N, et al. Brainstem circuits regulating gastric function[J]. Annu Rev Physiol, 2006, 68:279-305. BUYSE M, OVESJÖ M L, GOÏOT H, et al. Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve[J]. Eur J Neurosci, 2001, 14(1):64-72. |
| Contributed Indexing: | Keywords: Dorsal vagal complex; Electroacupuncture; Food intake; Leptin receptor; Obesity Local Abstract: [Publisher, Chinese] 目的: 观察背侧迷走神经复合体（DVC）中的瘦素受体（LepR）在电针调控摄食中的作用，探讨电针改善代谢障碍的中枢机制。方法: 随机选取10只C57BLKS/JGpt小鼠作为正常组，剩余C57BLKS/JGpt小鼠采用高脂饲料喂养构建食源性肥胖模型，将造模成功的小鼠随机分为高脂组、电针组，每组10只。电针组取“足三里”进行电针干预，20 min/次，每日1次，每周6次，共治疗5周。检测小鼠体质量、摄食量，肝脏、腹股沟白色脂肪组织（iWAT）、附睾白色脂肪组织（eWAT）和肩胛间棕色脂肪组织（BAT）质量，测定血清胰岛素、瘦素、空腹血糖，进行腹腔葡萄糖耐量实验（IPGTT）;免疫荧光染色法检测孤束核（NTS）和迷走神经背核（DMV）中LepR与原癌基因c-Fos蛋白（c-Fos）共表达、磷酸化信号转导子和转录激活子3（p-STAT3）表达及DMV中胆碱乙酰转移酶（ChAT）与c-Fos共表达。结果: 与正常组比较，高脂组体质量及肝脏、iWAT、eWAT、BAT湿重，血清胰岛素和瘦素，空腹血糖，IPGTT中60、90、120 min的血糖值，糖耐量曲线下面积（AUC）均升高（P<0.01）;NTS和DMV中LepR与c-Fos共表达、DMV的p-STAT3表达及ChAT与c-Fos共表达均降低（P<0.05，P<0.01）。与高脂组比较，电针组摄食量、体质量，肝脏、iWAT、eWAT、BAT湿重，血清瘦素，空腹血糖，IPGTT中60、90、120 min的血糖值，糖耐量AUC均降低（P<0.01）;NTS和DMV中LepR与c-Fos共表达、DMV的p-STAT3及ChAT与c-Fos共表达升高（P<0.05，P<0.01）。结论: 电针“足三里”可能通过增加肥胖小鼠DVC的LepR，修复迷走中枢信号，从而抑制摄食。. |
| Substance Nomenclature: | 0 (Receptors, Leptin) 0 (Leptin) 0 (Insulin) 0 (Proto-Oncogene Proteins c-fos) |
| Entry Date(s): | Date Created: 20260722 Date Completed: 20260722 Latest Revision: 20260722 |
| Update Code: | 20260722 |
| DOI: | 10.13702/j.1000-0607.20250778 |
| PMID: | 42482580 |
| Database: | MEDLINE |
| ISSN: | 1000-0607 |
|---|---|
| DOI: | 10.13702/j.1000-0607.20250778 |