利拉鲁肽对高脂诱导肥胖小鼠瘦素、脂肪分布及含量的影响

doi:10.6040/j.issn.1671-7554.0.2016.211

摘要/Abstract

摘要： 目的观察利拉鲁肽对高脂诱导的C57BL/6小鼠肥胖模型瘦素、体内脂肪含量及分布的影响。方法 4周龄C57BL/6小鼠60只,随机分为正常对照组(n=15)和高脂喂养组(n=45)。高脂喂养组给予40%脂肪含量高脂饲料喂养,正常对照组给予普通饲料喂养,构建肥胖小鼠模型至20周龄时,将造模成功的高脂喂养组随机分为利拉鲁肽组、饮食干预组(普通饲料喂养)和继续高脂喂养组(高脂饲料喂养),每组15只。利拉鲁肽组腹腔注射利拉鲁肽(稀释于双蒸水中)［100 μg/(kg·d)］,饮食干预组、继续高脂喂养组和正常对照组腹腔注射生理盐水［0.017 mL/(kg·d)］。监测记录各组体质量。药物干预12周后于10%水合氯醛麻醉下处死全部小鼠,利用磁共振测定小鼠体内脂肪含量,采用竞争法测定外周血瘦素含量,酶法测定外周血血脂水平。结果利拉鲁肽组体质量最低,与正常对照组、饮食干预组、继续高脂喂养组相比差异有统计学意义(P<0.05);利拉鲁肽组瘦素水平下降,与饮食干预组、继续高脂喂养组差异有统计学意义(P<0.05);利拉鲁肽组血脂水平下降,甘油三酯含量与正常对照组、继续高脂喂养组相比差异有统计学意义(P<0.05),总胆固醇含量仅与继续高脂喂养组差异有统计学意义(P<0.05);利拉鲁肽组脂肪总含量、肠系膜脂肪、附睾脂肪、肾周脂肪、肩胛下脂肪、皮下脂肪与其他各组比较均差异有统计学意义(P<0.05)。结论利拉鲁肽可明显减轻肥胖小鼠的体质量、降低瘦素水平,有降脂和调节脂肪分布的作用。

关键词: 肥胖, 高脂, 利拉鲁肽, 体脂分布, 瘦素, 磁共振

Abstract: Objective To observe the effect of liraglutide on the distribution of leptin and fat in high-fat diet induced C57BL/6 obese mice model. Methods A total of 60 C57BL/6 mice aged 4 weeks, body weight(14.03+0.92)g were randomly divided into 2 groups: high-fat diet(40% fat)group(n=45)and normal chow diet(4% fat)group(n=15). The body weight was recorded once a week until the obese mice models were built. Then the 45 obese mice in the high-fat diet group models were randomly divided into 3 groups: liraglutide group［intraperitoneal injection of 100 μg/(kg·d), n=15 ］, transferred normal diet group［intraperitoneal injection of 0.017 mL/(kg·d), n=15)］ and high fat diet group(n=15). During the 12-week intervention, the body weight of all animals was recorded. The fat content and leptin were monitored by magnetic resonance imaging and enzyme-linked immunosorbent assay. Results The liraglutide group had the lowest body weight than the other 3 groups(P<0.05). The liraglutide group had reduced degree of leptin compared with transferred normal diet group and high fat diet group(P<0.05). The liraglutide group 山东大学学报 (医学版)54卷8期 -沙莎,等.利拉鲁肽对高脂诱导肥胖小鼠瘦素、脂肪分布及含量的影响 \=-had lower serum lipid level; the triglycerides level was significantly lower than that in the normal chow diet group and high fat diet group(P<0.05); and the total cholesterol level was significantly lower than that in high fat diet group(P<0.05). The liraglutide group was different from the other groups in the mesenteric, epididymal, perirenal, subscapular and subcutaneous fat(P<0.05). Conclusion Liraglutide can significantly reduce the body weight and leptin degree in obese mice and has an effect on regulating lipid and fat distribution.

Key words: Magnetic resonance imaging, Obesity, High fat diet, Liraglutide, Fat content, Leptin

中图分类号:

R589.2

沙莎,Chowdhury Sumon Rahman,陈丽,何芹,张婧,范珊珊,孙磊. 利拉鲁肽对高脂诱导肥胖小鼠瘦素、脂肪分布及含量的影响[J]. 山东大学学报（医学版）, 2016, 54(8): 22-27.

SHA Sha, Chowdhury Sumon Rahman, CHEN Li, HE Qin, ZHANG Jing, FAN Shanshan, SUN Lei. Effect of liraglutide on leptin and fat content in high fat diet induced obese mice[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(8): 22-27.

参考文献

[1] Straub RH. Insulin resistance, selfish brain, and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases[J]. Arthritis Res Ther, 2014, 16(2): 4.
[2] Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance[J]. J Clin Invest, 2003, 112(12):1821-1830.
[3] Stabroth-Akil D, Leifeld L, Pfutzer R, et al. The effect of body weight on the severity and clinical course of ulcerative colitis[J]. Int J Colorectal Dis, 2014, 30(2): 237-242.
[4] Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism[J]. Am J Physiol Endocrinol Metab, 2003, 284(4): 671-678.
[5] Ashcroft FM, Rorsman P. Diabetes mellitus and the beta cell: the last ten years[J]. Cell, 2012, 148(6): 1160-1171.
[6] Inagaki-Ohara K, Okamoto S, Takagi K, et al. Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice[J]. Nutr Metab(Lond), 2016, 13: 7. doi: 10.1186/s12986-016-0066-1.
[7] Iepsen EW, Torekov SS, Holst JJ. Liraglutide for type 2 diabetes and obesity: a 2015 update[J]. Expert Rev Cardiovasc Ther, 2015, 13(7): 753-767.
[8] 申瑞玲, 马婧. 四种肥胖动物造模方法的比较[J]. 动物医学进展, 2007, 28(3): 105-108.
[9] Bi Y, Zhang B, Xu W, et al. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributionsin drug-naive subjects with type 2 diabetes[J]. Acta Diabetol, 2014, 51(5): 865-873.
[10] de Git KC, Adan RA. Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation[J]. Obes Rev, 2015, 16(3): 207-224.
[11] Tian YF, Chang WC, Loh CH, et al. Leptin-mediated inflammatory signaling crucially links visceral fat inflammation to obesity-associated β-cell dysfunction[J]. Life Sci, 2014, 116(1): 51-58.
[12] Noyan-Ashraf MH, Shikatani EA, Schuiki I, et al. A glucagon-like peptide-1 analog reverses the molecular pathology and cardiac dysfunction of a mouse model of obesity[J]. Circulation, 2013, 127(1): 74-85.
[13] 李龙辉, 李伶, 杨刚毅, 等. 利拉鲁肽对低脂联素血症小鼠胆固醇代谢相关基因的影响[J]. 中华内分泌代谢杂志, 2011, 27(7): 599-603. LI Longhui, LI Ling, YANG Gangyi, et al. Effect of liraglutide on the expression of genesrelated to cholesterol metabolism in ApoE mice with hypoadiponectinemia[J]. Chin J Endocrinol Metab, 2011, 27(7): 599-603.
[14] Linnemann AK, Neuman JC, Battiola TJ, et al. Glucagon-like peptide-1 regulates cholecystokinin production in β-Cells to protect from apoptosis[J]. Mol Endocrinol, 2015, 29(7): 978-987.
[15] Barreto-Vianna AR, Aguila MB, Mandarim-de-Lacerda CA. Effects of liraglutide in hypothalamic arcuate nucleus of obese mice[J]. Obesity(Silver Spring), 2016, 24(3): 626-633.
[16] Kanoski SE, Ong ZY, Fortin SM, et al. Liraglutide, leptin and their combined effects on feeding: additive intake reduction through common intracellular signalling mechanisms[J]. Diabetes Obes Metab, 2015, 17(3): 285-293.
[17] Scotece M, Abella V, López V, et al. An update on leptin as immunomodulator[J]. Expert Rev Clin Immunol, 2014, 10(9): 1165-1170.
[18] Clemmensen C, Chabenne J, Finan B, et al. GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet[J]. Diabetes, 2014, 63(4): 1422-1427.
[19] Mostafa AM, Hamdy NM, El-Mesallamy HO, et al. Glucagon-like peptide 1(GLP-1)-based therapy upregulates LXR-ABCA1/ABCG1 cascade in adipocytes[J]. Biochem Biophys Res Commun, 2015, 468(4): 900-905.
[20] Iepsen EW, Lundgren J, Dirksen C, et al. Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss[J]. Int J Obes(Lond), 2015, 39(5): 834-841.
[21] Kooijman S, Wang Y, Parlevliet ET, et al. Central GLP-1 receptor signalling accelerates plasma clearance of triacylglycerol and glucose by activating brown adipose tissue in mice[J]. Diabetologia, 2015, 58(11): 2637-2646.
[22] Armstrong MJ, Hull D, Guo K, et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis[J]. J Hepatol, 2016, 64(2): 399-408.
[23] López M, Diéguez C, Nogueiras R. Hypothalamic GLP-1: the control of BAT thermogenesis and browning of white fat[J]. Adipocyte, 2015, 4(2): 141-145.
[24] Wei Q, Li L, Chen JA, et al. Exendin-4 improves thermogenic capacity by regulating fat metabolism on brown adipose tissue in mice with diet-induced obesity[J]. Ann Clin Lab Sci, 2015, 45(2): 158-165.
[25] Chae YN, Kim TH, Kim MK, et al. Beneficial effects of evogliptin, a novel dipeptidyl peptidase 4 inhibitor, on adiposity with increased ppargc1a in white adipose tissue in obese mice[J]. PLoS One, 2015, 10(12): e0144064. doi: 10.1371/journal.pone.0144064.

相关文章 15

[1]	王韶卿刘毅慧付婷婷成金勇刘强. 肝癌³¹磷磁共振波谱数据的分类[J]. 山东大学学报(医学版), 2209, 47(6): 42-46.
[2]	张媛李英敏冯月秋常彩云潘华伟王束玫. 血清脂联素水平与肥胖、胰岛素抵抗的关系探讨[J]. 山东大学学报(医学版), 2209, 47(6): 124-.
[3]	赵万霞,詹群璋,金婷,刘玉新,曲崇正,吴剑纯. 基于孟德尔随机化分析肠道菌群、血液代谢物和肥胖的因果关系[J]. 山东大学学报 (医学版), 2026, 64(4): 72-82.
[4]	金晨曦,沈薇,李娜,孙建锋,杨驰,郭泾. ADDWoR关节镜下盘复位术盘-髁运动的定量分析[J]. 山东大学学报 (医学版), 2025, 63(7): 54-61.
[5]	王磊,常霄,王梓萌,李娇娇,崔书君,杨飞,朱月香. 瘤内及瘤周DCE-MRI影像组学对宫颈癌患者无进展生存期的预测价值[J]. 山东大学学报 (医学版), 2025, 63(6): 45-54.
[6]	单体晓,杜韦辰,王勤周,李安宁,李春海. 自身免疫性郎飞结病磁共振成像研究进展[J]. 山东大学学报 (医学版), 2025, 63(11): 117-122.
[7]	刘晶晶,庞婧,赵晓丹,林昕,付敏,陈静静. 基于乳腺X线摄影及DCE-MRI机器学习模型预测乳腺癌新辅助治疗后病理完全缓解:双中心研究[J]. 山东大学学报 (医学版), 2025, 63(1): 60-72.
[8]	冯悦,俞一凡,吴思佳,李洪凯,薛付忠. 内脏脂肪组织与肺部疾病的孟德尔随机化研究[J]. 山东大学学报 (医学版), 2024, 62(7): 48-55.
[9]	刘小文,曹永泉,侯明源,于德新. EOB-MRI多定量参数对肝胆期乏血供低信号结节进展风险的评估价值[J]. 山东大学学报 (医学版), 2024, 62(4): 31-39.
[10]	刘雯,冯文娟,杨阳,纪昌丽,晁岚. 体质量指数对卵巢正常反应患者累积分娩率的影响[J]. 山东大学学报 (医学版), 2024, 62(3): 54-60.
[11]	许沛晨,李晓博,庄向华,娄能俊,吕丽,周玲雁,牟亚朋,宋玉文,陈诗鸿. 儿童Alstrom综合征2例并文献复习[J]. 山东大学学报 (医学版), 2024, 62(3): 107-111.
[12]	梁中昊,庄向华,黄珊,韩晓琳,华梦羽,琚丽萍,陈诗鸿. 饮食诱导肥胖雌鼠棕色脂肪组织蛋白质组学分析[J]. 山东大学学报 (医学版), 2024, 62(2): 10-19.
[13]	吴思雨,沈业隆,王锡明. 影像组学预测原发性中枢神经系统淋巴瘤的Ki-67标记指数[J]. 山东大学学报 (医学版), 2024, 62(11): 67-72.
[14]	范佳旭, 成芳,乔俊鹏,费海程,陈学禹,赵云,贾红英. 中介或混杂因素:是否应调整肥胖以估计三卤甲烷对甲状腺功能的影响[J]. 山东大学学报 (医学版), 2024, 62(1): 102-110.
[15]	靳新娟,左立平,邓展昊,李安宁,于德新. MRI影像组学对135例肝癌耐药蛋白PFKFB3的预测价值[J]. 山东大学学报 (医学版), 2023, 61(6): 79-86.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed