Fas凋亡抑制分子FAIM 1表达缺失诱发单纯性肥胖的初步研究

doi:10.13523/j.cb.20170606

中国生物工程杂志

2017, Vol. 37

Issue (6): 37-42 DOI: 10.13523/j.cb.20170606

研究报告

Fas凋亡抑制分子FAIM 1表达缺失诱发单纯性肥胖的初步研究

李艳伟¹, 马义¹, 韩磊¹, 肖兴¹, 党诗莹¹, 文涛¹, 王得华¹, 范志勇²

1. 暨南大学细胞生物学系暨南大学生物医药研究院广东省生物工程药物重点实验室基因工程药物国家工程研究中心广州 510632;
2. 广州中医药大学第二附属医院<广东省中医院> 广州 510405

A Preliminary Study on Fas Apoptosis Inhibitory Molecule FAIM 1 Inducing and Simple Obesity

LI Yan-wei¹, MA Yi¹, HAN Lei¹, XIAO Xing¹, DANG Shi-ying¹, WEN Tao¹, WANG De-hua¹, FAN Zhi-yong²

1. Department of Cell Biology of Jinan University, Institute of Biological Medicine of Jinan University, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China;
2. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510632, China

全文: PDF(526 KB) HTML

摘要： 利用肥胖患者血液和肥胖动物模型研究Fas凋亡抑制分子FAIM 1与单纯性肥胖的关系，为揭示单纯性肥胖发生的分子机理和诊治肥胖提供新的实验基础。检测40例单纯性肥胖患者和17例正常者血液白细胞的FAIM 1蛋白的表达量，分析FAIM 1与单纯性肥胖的相关性。为进一步揭示FAIM 1与单纯性肥胖发生、发展的内在关系，利用高脂饲料建立肥胖模型，并测定肥胖组和对照组大鼠的体重和血糖水平；造模成功的肥胖组大鼠和对照组大鼠禁食12h，麻醉心脏取血，分析血脂中总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白-胆固醇（HDL-C）和低密度脂蛋白-胆固醇（LDL-C）的变化；取肥胖组和对照组大鼠的附睾脂肪垫和肾周脂肪，分析重量变化；取肥胖组和对照组大鼠，利用Western-blot 检测FAIM 1及胰岛素受体β（IR β）的表达变化。实验结果表明：与正常者相比，单纯性肥胖患者血液白细胞的FAIM 1表达量平均减少36.4%；与对照组相比，肥胖组大鼠血清TC、TG和LDL-C分别增加37.1%、25.6%和39.1%，而HDL-C则降低33.3%；肥胖组大鼠附睾脂肪垫和肾周脂肪分别是对照组的1.85倍和2.24倍；与对照组相比，肥胖组大鼠肝脏FAIM 1、IRβ的表达量分别降低45.9%和32.6%，与临床血液样本的检测结果一致。研究表明，FAIM 1表达与单纯性肥胖发生具有显著的负相关性，FAIM 1可成为单纯性肥胖诊断和治疗的新靶点。

关键词： 高脂饮食; 胰岛素受体β; 临床血液; 肥胖; Fas凋亡抑制分子

Abstract: The relationship between Fas apoptosis inhibitory molecule FAIM 1 and simple obesity was studied by using the blood of obese patients and the model of obese rats to provide the new experimental basis for revealing the molecular mechanism of obesity and the diagnosis and treatment for obesity. The correlation between FAIM 1 expression and simple obesity was determined through testing the expression of FAIM 1 protein in white blood cells for 17 cases of normal individuals and 40 cases of obese patients. To further reveal the relationship between FAIM1 and the occurrence and development of simple obesity, the model of obese rats was established by using high-fat diet, and the body weight and blood glucose levels of obese and control rats were measured. The successfully constructed obese model rats and normal rats were fasted for 12 hours. Blood taken from heart were used to measure the change of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) after anesthetizing animals. The epididymal fat pad and perirenal fat weights of obese rats and control rats were analyzed. The expression changes of FAIM 1 and insulin receptor beta (IR β) protein were detected by Western blot. The results showed the expression of FAIM1 protein in white blood cells of patients with simple obesity was reduced by 36.4% compared with normal control. Compared with the normal control rats, the serum levels of TC, TG and LDL-C in the obese model group were respectively increased by 37.1%, 25.6% and 39.1%, while HDL-C was reduced by 33.3%. The epididymal fat pad and perirenal fat weights of the obese model rats were respectively 1.85- and 2.24-fold of that in the normal control rats. Compared with the control group, the expression of FAIM 1 and IR β in the liver of obese rats were decreased by 45.9% and 32.6%, respectively, which was consistent with the results of clinical blood samples. So it displayed that the expression of FAIM 1 is significantly nagtively correlated with simple obesity, and FAIM 1 may be a new target for diagnosis and treatment for simple obesity.

Key words: Obesity High-fat diet Clinical blood Fas apoptosis inhibitory molecule (FAIM) Insulin Receptor β(IR β)

收稿日期: 2017-01-03 出版日期: 2017-06-25

ZTFLH:

Q819

基金资助: 国家自然科学基金（81373314，81473688）、广东省自然科学基金（2015A030313333，2015A030313345）、广东省科技计划（2014A020210015，2013B090500105）、中央高校基本科研业务费专项资金（21615412）、广州市科技计划（201707010245）资助项目

通讯作者: 马义 E-mail: tmayi@jnu.edu.cn

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	马义
	肖兴
	文涛
	王得华
	韩磊
	党诗莹
	范志勇
	李艳伟

引用本文:

李艳伟, 马义, 韩磊, 肖兴, 党诗莹, 文涛, 王得华, 范志勇. Fas凋亡抑制分子FAIM 1表达缺失诱发单纯性肥胖的初步研究[J]. 中国生物工程杂志, 2017, 37(6): 37-42.

LI Yan-wei, MA Yi, HAN Lei, XIAO Xing, DANG Shi-ying, WEN Tao, WANG De-hua, FAN Zhi-yong. A Preliminary Study on Fas Apoptosis Inhibitory Molecule FAIM 1 Inducing and Simple Obesity. China Biotechnology, 2017, 37(6): 37-42.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20170606 或 https://manu60.magtech.com.cn/biotech/CN/Y2017/V37/I6/37

[1] Krammer P H. CD95's deadly mission in the immune system. Nature, 2000, 407(6805):789-795.
[2] Schneider T J, Fischer G M, Donohoe T J, et al. A novel gene coding for a Fas apoptosis inhibitory molecule (FAIM) isolated from inducibly Fas-resistant B lymphocytes. Journal of Experimental Medicine, 1999, 189(6):949-956.
[3] Planells-Ferrer L, Urresti J, Coccia E, et al. Fas apoptosis inhibitory molecules:more than death-receptor antagonists in the nervous system. Journal of Neurochemistry, 2016, 139(1):11-21.
[4] Sole C, Dolcet X, Segura M F, et al. The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling. Journal of Cell Biology, 2004, 167(3):479-492.
[5] Zhong X, Schneider T J, Cabral D S, et al. An alternatively spliced long form of Fas apoptosis inhibitory molecule (FAIM) with tissue-specific expression in the brain. Molecular Immunology, 2001, 38(1):65-72.
[6] Huo J, Xu S, Lam K P. Fas apoptosis inhibitory molecule regulates T cell receptor-mediated apoptosis of thymocytes by modulating Akt activation and Nur77 expression. Journal of Biological Chemistry, 2010, 285(16):11827-11835.
[7] Huo J, Xu S, Guo K, et al. Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes. Cell Death & Differentiation, 2009, 16(7):1062-1070.
[8] Huo J, Ma Y, Liu J J, et al. Loss of Fas apoptosis inhibitory molecule leads to spontaneous obesity and hepatosteatosis. Cell Death and Disease, 2016, 7(2):e2091.
[9] Wigand J P, Blackard W G. Downregulation of insulin receptors in obese man. Diabetes, 1979,28(4):287-291.
[10] Arner P, Einarsson K, Backman L, et al. Studies of liver insulin receptors in non-obese and obese human subjects. J Clin Invest, 1983, 72(5):1729-1736.
[11] McElduff A, Hedo J A, Taylor S I, et al. Insulin receptor degradation is accelerated in cultured lymphocytes from patients with genetic syndromes of extreme insulin resistance. J Clin Invest, 1984, 74(4):1366-1374.
[12] Qian B C, Shi H, Lu Y P. Progress in studies of preparation of obesity animal models. Chinese Journal of New Drugs, 2007, 16(15):1159-1162.
[13] Carriba P, Jimenez S, Navarro V, et al. Amyloid-beta reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFalpha from neuronal protection to death. Cell Death & Disease, 2015, 6(2):e1639.
[14] Huo J, Xu S, Lin B, et al. Fas apoptosis inhibitory molecule is upregulated by IGF-1 signaling and modulates Akt activation and IRF4 expression in multiple myeloma. Leukemia Official Journal of the Leukemia Society of America Leukemia Research Fund U K, 2012, 27(5):1165-1171.
[15] Huo J, Xu S, Lin B, et al. Fas apoptosis inhibitory molecule is upregulated by IGF-1 signaling and modulates Akt activation and IRF4 expression in multiple myeloma. Leukemia Official Journal of the Leukemia Society of America Leukemia Research Fund U K, 2012, 27(5):1165-1171.
[16] Huo J, Xu S, Guo K, et al. Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes. Cell Death & Differentiation, 2009, 16(7):1062-1070.

[1]	曾祥意,潘杰. 自噬调控白色脂肪细胞棕色化的研究进展 ^*[J]. 中国生物工程杂志, 2020, 40(6): 63-73.
[2]	冯琳晶,于洋,杜红伟. FoxO1在胰岛β细胞代谢灵活性受损及失代偿进程中的作用 ^*[J]. 中国生物工程杂志, 2018, 38(6): 70-76.
[3]	孟建华. Cetus等公司开发TNF作为肥胖抑制剂[J]. 中国生物工程杂志, 1987, 7(5): 80-80.

Viewed

Full text

Abstract

Cited

Shared

Discussed