LKB1-AMPKα-SIRT1信号通路在奶牛脂肪组织脂代谢中的调控作用

doi:10.13560/j.cnki.biotech.bull.1985.2018-0707

摘要/Abstract

摘要： 奶牛脂肪细胞体积和数目的不断增加会导致脂肪组织脂代谢的紊乱,引起一系列相关慢性疾病如Ⅱ型糖尿病、酮病、脂肪肝、高脂血症等的发生,LKB1-AMPKα-SIRT1信号通路在奶牛脂肪组织脂代谢中起着重要的调控作用。单磷酸腺苷活化蛋白激酶（AMPK）是比较保守的丝氨酸/苏氨酸激酶,在调节能量代谢中起着枢纽作用。肝激酶B1（LKB1）属于一种丝氨酸激酶,是AMPKα的上游激酶,可参与细胞内能量代谢等多种生物活动。沉默信息调节因子1（SIRT1）是一种NAD⁺依赖的组蛋白去乙酰化酶,可通过去乙酰化LKB1增加AMPKα的活性。就LKB1-AMPKα-SIRT1信号转导通路在奶牛脂肪组织脂代谢紊乱中的调控机制作一综述,旨在为下一步研究奶牛脂代谢相关信号通路调控机理提供依据。

关键词: LKB1, AMPKα, SIRT1, 奶牛, 脂肪组织, 脂质代谢

Abstract: The increasing volume and number of adipocyte leads to disorder of lipid metabolism in adipose tissue,which causes different chronic diseases such as type II diabetes,ketosis,fatty liver,and hyperlipidemia. The LKB1-AMPKα-SIRT1 signal pathway plays important regulating role in the lipid metabolism of dairy cows adipose tissue. AMPK as conservative serine/threonine kinase plays a pivotal role in the regulation of energy metabolism. LKB1（liver kinase B1）is a serine/threonine kinase,an upstream kinase of AMPKα,participates in various biological activities such as intracellular energy metabolism. Silencing information regulator factor 1（SIRT1）,a kind of NAD⁺-dependent histone deacetylase,can increase AMPKα activity by deactivating LKB1. This article reviews the regulation mechanisms of LKB1-AMPKα-SIRT1 signal transduction pathways in lipid metabolism of adipose tissue in dairy cows,aiming at providing a basis for further studying the regulating mechanisms of related signal pathways in the lipid metabolism of dairy cows.

Key words: LKB1, AMPKα, SIRT1, dairy cows, adipose tissue, lipid metabolism

明鹏飞, 黄莹莹, 董妍丽, 聂星灿, 冯士彬, 王希春, 程建波, 李锦春, 吴金节, 李玉. LKB1-AMPKα-SIRT1信号通路在奶牛脂肪组织脂代谢中的调控作用[J]. 生物技术通报, 2019, 35(2): 176-181.

MING Peng-fei, HUANG Ying-ying, DONG Yan-li, NIE Xing-can, FENG Shi-bin, WANG Xi-chun, CHENG Jian-bo, LI Jin-chun, WU Jin-jie, LI Yu. Regulation of LKB1-AMPKα-SIRT1 Signal Pathway in Lipid Metabolism in the Adipose Tissue of Dairy Cows[J]. Biotechnology Bulletin, 2019, 35(2): 176-181.

参考文献

[1] Deguchi A, Miyoshi H, Kojima Y, et al.LKB1 suppresses p21-activated kinase-1(PAK1)by phosphorylation of thr(109)in the p21-binding domain[J]. Journal of Biological Chemistry, 2010, 285(24):18283-18290.
[2] 陈标, 满玉蓉, 高柳玲, 等. AMPK调控能量代谢研究进展[J]. 生物学杂志, 2017, 34(5):78-82.
[3] 李莉萍, 曾卫民, 郭明日. SIRT1的生物学功能及其在胰岛素抵抗中的作用[J]. 生命科学研究, 2010, 14(4):372-376.
[4] 韩洁. LKB1抑制脂肪生成和分化的机制研究[D]. 天津:天津医科大学, 2016.
[5] Zeqiraj E, Filippi BM, Deak M, et al.Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation[J]. Science, 2009, 326(5960):1707-1711.
[6] Zhang BB, Zhou G, Li C.AMPK:an emerging drug target for diabetes and the metabolic syndrome[J]. Cell Metabolism, 2009, 9(5):407-416.
[7] 张霞, 孙琳琳, 钟殿胜. LKB1-AMPK-mTOR信号传导通路在肿瘤中的研究进展[J]. 中国肺癌杂志, 2011, (8):685-688.
[8] Eggers C, Kline E, Zhong D, et al.STE20-related kinase adaptor protein α(STRADα)regulates cell polarity and invasion through PAK1 signal in LKB1-null cells[J]. Journal of Biological Chemistry, 2012, 287(22):18758-18768.
[9] Kováčik J, Kalafová A, Tušimová E.Relations between selected indicators of blood and milk of dairy cows with metabolic disorders[J]. Journal of Microbiology Biotechnology & Food Sciences, 2013, (2):1980-1987.
[10] 李心慰. 乙酸、非酯化脂肪酸、生长激素和催乳素调控奶牛肝细胞脂代谢的信号机制[D]. 长春:吉林大学, 2013.
[11] Hardie DG.AMPK:positive and negative regulation, and its role in whole-body energy homeostasis[J]. Current Opinion in Cell Biology, 2015(33):1-7.
[12] 耿凤豪, 张鹏, 董玲, 等. AMPK-能量代谢感受器与可激活AMPK相关的药物研究进展[J]. 心脏杂志, 2014(1):97-100.
[13] 张玉佩, 杨钦河, 邓远军, 等. 参苓白术散对高脂饮食诱导的NAFLD大鼠肝组织超微结构及AMPKα磷酸化的影响[J]. 中药药理与临床, 2016(1):6-10.
[14] Lim JH, Gerharthines Z, Dominy JE, et al.Oleic acid stimulates complete oxidation of fatty acids through protein kinase a-dependent activation of sirt1-pgc1α complex[J]. Journal of Biological Chemistry, 2013, 288(10):7117-7126.
[15] Guarente L.Sirtuins as potential targets for metabolic syndrome[J]. Nature, 2006, 444(7121):868-874.
[16] Ramsey K, Mills K, Satoh A, et al.Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing(BESTO)mice[J]. Aging Cell, 2008, 7(1):78-88.
[17] Kim H, Mendez R, Chen X, et al.Lysine acetylation of crebh regulates fasting-induced hepatic lipid metabolism[J]. Molecular & Cellular Biology, 2016, 35(24):4121-4134.
[18] 邵芳, 郁建锋, 张燕萍, 等. SIRT1基因的表达调控及对动物脂类代谢的功能[J]. 常熟理工学院学报, 2015, 29(4):8-14.
[19] 邓清华. NEFAs对犊牛原代肝细胞糖脂代谢的调控机制[D]. 长春:吉林大学, 2015.
[20] 倪鸣, 王金焱, 王璟. 白色脂肪组织棕色化调控机制的研究进展[J]. 医学研究生学报, 2015(7):771-775.
[21] 秦佑. 树豆酮酸A抑制3T3-L1脂肪细胞分化及调控其脂质代谢的作用研究[D]. 广州:广州中医药大学, 2016.
[22] 张世奇. PLIN1对奶牛脂肪细胞脂代谢及炎性细胞因子合成的影响[D]. 长春:吉林大学, 2017.
[23] 黄文钰, 李向平. 脂肪细胞三酰甘油分解代谢相关调节的研究进展[J]. 临床与病理杂志, 2013, 33(3):230-234.
[24] 宋宇宙. 牛蒡子苷元通过AMPK信号通路调节脂肪代谢的作用研究[D]. 广州:广州中医药大学, 2017.
[25] 殷立恒. PRL、GC对奶牛脂肪细胞和肝细胞脂代谢的影响[D]. 长春:吉林大学, 2015.
[26] Cantãó C, Gerhart-Hines Z, Feige JN, et al.AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity[J]. Nature, 2009, 458(7241):1056-1060.
[27] 梁舒. 小檗碱通过Sirt1改善3T3--L1脂肪细胞糖代谢的机制研究[D]. 南京:南京中医药大学, 2017.
[28] Hardie DG, Hawley SA, Scott JW.AMP-activated protein kinase-development of the energy sensor concept[J]. Journal of Physiology, 2010, 574(1):7-15.
[29] 孟胜喜, 冯琴, 彭景华, 等. BZL方对游离脂肪酸诱导HepG2细胞脂肪沉积和LKB1-AMPK-ACC信号传导通路的影响[J]. 中华中医药杂志, 2014(5):1391-1396.
[30] 匡霞, 陆付耳, 易屏. 小檗碱对HepG2胰岛素抵抗细胞模型中LKB1-AMPK-TORC2信号网络的影响[J]. 中国中西医结合消化杂志, 2015(7):467-471.
[31] Li X, Li X, Chen H, et al.Non-esterified fatty acids activate the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes[J]. Cell Biochemistry & Biophysics, 2013, 67(3):1157-1169.
[32] Li X, Li Y, Ding H, et al.Insulin suppresses the AMPK signaling pathway to regulate lipid metabolism in primary cultured hepatocytes of dairy cows[J]. Journal of Dairy Research, 2018, (85):157-162.
[33] 高晓娜, 郭小权. 一磷酸腺苷激活的蛋白激酶对动物糖脂代谢的调节作用[J]. 动物营养学报, 2017, 29(12):4287-4294.
[34] 李琳, 郑卓, 贺红专. PPARγ基因调控猪脂肪沉积研究进展[J]. 中国猪业, 2016, 11(8):57-60.
[35] 杜希良. miR-181a对犊牛原代肝细胞糖脂代谢稳态的调控机制[D]. 长春:吉林大学, 2016.
[36] Bellet MM, Nakahata Y, Boudjelal M, et al.Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1[J]. Proc Natil Acad Sci USA, 2013, 110(9):3333-3338.
[37] Liu L, Li X, Li Y, et al.Effects of nonesterified fatty acids on the synthesis and assembly of very low density lipoprotein in bovine hepatocytes in vitro[J]. Journal of Dairy Science, 2014, 97(3):1328-1335.
[38] Ito M, Nagasawa M, Omae N, et al.A novel JNK2/SREBP-1c pathway involved in insulin-induced fatty acid synthesis in human adipocytes[J]. Journal of Lipid Research, 2013, 54(6):1531-1540.
[39] Zhang M, Zhang S, Hui Q, et al.β-hydroxybutyrate facilitates fatty acids synthesis mediated by sterol regulatory element-binding protein1 in bovine mammary epithelial cells[J]. Cellular Physiology & Biochemistry, 2015, 37(6):2115-2124.
[40] Chau MD, Gao J, Yang Q, et al.Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway[J]. Proc Natil Acad Sci USA, 2010, 107(28):12553-12558.
[41] Li X, Chen H, Guan Y, et al.Acetic acid activates the AMP-activated protein kinase signal pathway to regulate lipid metabolism in bovine hepatocytes[J]. Journal of Steroid Biochemistry & Molecular Biology, 2013, 138(7):445-454.
[42] 王怡, 刘宗平. 奶牛围产期脂肪代谢的研究进展[J]. 畜牧与兽医, 2013, 45(4):98-101.
[43] 孙艳发, 张敏, 李焰, 等. 维生素E对动物脂肪代谢调控的研究进展[J]. 中国畜牧杂志, 2015, 51(13):82-85.
[44] Shi X, Li D, Deng Q, et al.Acetoacetic acid induces oxidative stress to inhibit the assembly of very low density lipoprotein in bovine hepatocytes[J]. Journal of Dairy Research, 2016, 83(4):442-446.
[45] Ono K, Horie T, Nishino T, et al.MicroRNA-33a/b in lipid metabolism-novel “thrifty” models[J]. Circulation Journal Official Journal of the Japanese Circulation Society, 2015, 79(2):278-284.
[46] 靳青, 魏晨, 张相伦, 等. miRNA-33对胆固醇合成的调控作用及其在肉牛上的研究进展[J]. 草食家畜, 2018(4):5-9.