|本期目录/Table of Contents|

[1]孙亚朝,邓邦利,牛文彦.短链脂肪酸对肝细胞糖脂代谢调节的作用机制研究[J].天津医科大学学报,2023,29(02):126-130.
 SUN Ya-zhao,DENG Bang-li,NIU Wen-yan.Study of the mechanism of short chain fatty acids-regulated glucose and lipid metabolism in hepatocytes[J].Journal of Tianjin Medical University,2023,29(02):126-130.
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短链脂肪酸对肝细胞糖脂代谢调节的作用机制研究(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
29卷
期数:
2023年02期
页码:
126-130
栏目:
基础医学
出版日期:
2023-03-20

文章信息/Info

Title:
Study of the mechanism of short chain fatty acids-regulated glucose and lipid metabolism in hepatocytes
文章编号:
1006-8147(2023)02-0126-05
作者:
孙亚朝邓邦利牛文彦
天津医科大学基础医学院免疫学系,天津300070
Author(s):
SUN Ya-zhaoDENG Bang-liNIU Wen-yan
Department of Immunology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China
关键词:
肝细胞短链脂肪酸AktGSK-3βAMPKACC
Keywords:
AML12Short chain fatty acidsAktGSK-3βAMPKACC
分类号:
R34
DOI:
-
文献标志码:
A
摘要:
目的:探究肠道菌群代谢产物短链脂肪酸对小鼠肝细胞AML12糖脂代谢的影响。方法:将AML12小鼠肝细胞分别在1、2、4、8和16mmol/L浓度的乙酸钠、丙酸钠和丁酸钠中孵育24h,Western印迹检测糖脂代谢信号通路中关键蛋白蛋白激酶B(Akt)、糖原合成酶激酶-3β(GSK-3β)、腺苷酸活化蛋白激酶(AMPK)和乙酰辅酶A羧化酶(ACC)的磷酸化水平以及AMPK总蛋白的表达量。结果:16mmol/L丙酸钠显著升高Akt磷酸化水平,为对照组的(1.56±0.09)倍(F=3.251,P<0.05),丁酸钠在8mmol/L时即可显著增加Akt的磷酸化,为对照组的(1.66±0.18)倍(F=8.249,P<0.05),而乙酸钠不影响Akt的磷酸化。8mmol/L丁酸钠即可显著上调GSK-3β的磷酸化水平,为对照组的(1.61±0.14)倍(F=4.690,P<0.05),而乙酸钠和丙酸钠不影响GSK-3β的磷酸化。乙酸钠、丙酸钠和丁酸钠在不影响AMPK总蛋白表达的情况下,分别在2、1、2mmol/L时即可显著升高AMPK磷酸化水平,分别为对照组的(1.40±0.13)倍(F=4.720,P<0.05)、(1.66±0.18)倍(F=16.54,P<0.05)和(1.70±0.13)倍(F=23.50,P<0.05)。乙酸钠、丙酸钠和丁酸钠分别在16、4、1mmol/L即可显著升高ACC磷酸化水平,分别为对照组的(2.01±0.30)倍(F=4.807,P<0.01)、(1.66±0.18)倍(F=7.507,P<0.05)和(1.79±0.06)倍(F=7.028,P<0.01)。结论:短链脂肪酸可能通过调节肝细胞Akt/GSK-3β和AMPK/ACC通路减少肝脏脂质积聚并降低血糖。
Abstract:
Objective:To investigate the role of short chain fatty acids produced by intestinal flora on glucose and lipid metabolism in mouse AML12 hepatocytes. Methods:AML12 mouse hepatocytes were incubated in 1,2,4,8 and 16 mmol/L concentrations of sodium acetate,sodium propionate and sodium butyrate for 24 hours,respectively. The level of p-protein kinase B (Akt),p-glycogen synthase kinase-3β (GSK-3β),p-AMP activated protein kinase (AMPK),p-acetyl-CoA carboxylase (ACC)and expression of AMPK were determined by Western blotting. Results:16 mmol/L sodium propionate significantly increased the phosphorylation of Akt [(1.56±0.09)-fold vs. control group](F=3.251,P<0.05),8 mmol/L sodium butyrate significantly phosphorylated Akt [(1.66±0.18)-fold vs. control group](F=8.249,P<0.05),while sodium acetate did not affect the level of p-Akt. 8 mmol/L sodium butyrate significantly increased the level of p-GSK-3β [(1.61±0.14)-fold vs. control group](F=4.690,P<0.05),while sodium acetate and sodium propionate did not affect p-GSK-3β. 2 mmol/L sodium acetate,1 mmol/L sodium propionate and 2 mmol/L sodium butyrate significantly increased the phosphorylation of AMPK[(1.40±0.13)-fold,(1.66±0.18)-fold,(1.70±0.13)-fold vs. control group,respectively)](all P<0.05;F=4.720,16.54,23.50)without affecting the expression of AMPK. 16 mmol/L sodium acetate,4 mmol/L sodium propionate and 1 mmol/L sodium butyrate significantly increased p-ACC [(2.01±0.30)-fold,(1.66±0.18)-fold,(1.79±0.06)-fold vs. control group,respectively](P<0.01,P<0.05,P<0.01;F=4.807,7.507,7.028). Conclusion:Short chain fatty acids have the potential role of regulation glucose and lipid metabolism and blood glucose via Akt/GSK-3β and AMPK/ACC signal pathway.

参考文献/References:

[1] International Diabetes Federation. IDF diabetes atlas ninth edition [EB/OL]. 2021:Available from:www. diabetesatlas.org.
[2] CARBONE S,DEL BUONO M G,OZEMEK C,et al. Obesity,risk of diabetes and role of physical activity,exercise training and car-diorespiratory fitness[J]. Prog Cardiovasc Dis,2019,62(4):327-333.
[3] FRANCISCO V,SANZ M J,REAL J T,et al. Adipokines in non-al-coholic fatty liver disease:are we on the road toward new biomarkers and therapeutic targets? [J]. Biology(Basel),2022,11(8):1237.
[4] MALESZA I J,MALESZA M,WALKOWIAK J,et al. High-fat, western-style diet,systemic inflammation,and gut microbiota:a nar-rative review [J]. Cells,2021,10(11):3164.
[5] FROST F. Introduction to the microbiome[J]. Inn Med(Heidelb), 2022,63(10):1015-1021.
[6] ABDUL RAHIM M B H,CHILLOUX J,MARTINEZ-GILI L,et al. Diet-induced metabolic changes of the human gut microbiome:im-portance of short-chain fatty acids,methylamines and indoles [J]. Acta Diabetol,2019,56(5):493-500.
[7] BIELKA W,PRZEZAK A,PAWLIK A. The role of the gut microbio-ta in the pathogenesis of diabetes [J]. Int J Mol Sci,2022,23(1):480.
[8] LYNCH S V,PEDERSEN O. The human intestinal microbiome in health and disease [J]. N Engl J Med,2016,375(24):2369-2379.
[9] LIU L,ZHANG J,CHENG Y,et al. Gut microbiota:a new target for T2DM prevention and treatment[J]. Front Endocrinol(Lausanne), 2022,13:958218.
[10] DOUMATEY A P,ADEYEMO A,ZHOU J,et al. Gut microbiome profiles are associated with type 2 diabetes in urban africans [J]. Front Cell Infect Microbiol,2020,10:63.
[11] LARROSA M,MARTíNEZ-LóPEZ S,GONZáLEZ-RODRíGUEZ L G,et al. Microbiota-diet interactions:towards personalized nutri-tion[J]. Nutr Hosp,2022,39(Spec No3):39-43.
[12] CRONIN P,JOYCE S A,O′TOOLE P W,et al. Dietary fibre modu-lates the gut microbiota[J]. Nutrients,2021,13(5):1655.
[13] UDAYAPPAN S D,HARTSTRA A V,DALLINGA-THIE G M,et al. Intestinal microbiota and faecal transplantation as treatment modali-ty for insulin resistance and type 2 diabetes mellitus [J]. Clin Exp Immunol,2014,177(1):24-29.
[14] CHADT A,AL-HASANI H. Glucose transporters in adipose tissue, liver,and skeletal muscle in metabolic health and disease [J]. Pflugers Arch,2020,472(9):1273-1298.
[15] SRIVANI G,SHARVIRALA R,VEERAREDDY P R,et al. GSK-3 inhibitors as new leads to treat type-Ⅱdiabetes[J]. Curr Drug Tar-gets,2021,22(13):1555-1567.
[16] ZHANG J,FENG Q. Pharmacological effects and molecular protec-tive mechanisms of astragalus polysaccharides on nonalcoholic fatty liver disease [J]. Front Pharmacol,2022,13:854674.
[17] ULLAH A,ALI N,AHMAD S,et al. Glycogen synthase kinase-3 (GSK-3)a magic enzyme:it's role in diabetes mellitus and glucose homeostasis,interactions with fluroquionlones. A mini-review [J]. Braz J Biol,2021,83:e250179.
[18] WANG L,LI J,DI L J. Glycogen synthesis and beyond,a comprehen-sive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases[J]. Med Res Rev, 2022,42(2):946-982.
[19] HUANG X,LIU G,GUO J,et al. The PI3K/AKT pathway in obesity and type 2 diabetes[J]. Int J Biol Sci,2018,14(11):1483-1496.
[20] ZHOU Y J,XU N,ZHANG X C,et al. Chrysin improves glucose and lipid metabolism disorders by regulating the AMPK/PI3K/AKT sig-naling pathway in insulin-resistant HepG2 cells and HFD/STZ-in-duced C57BL/6J Mice[J]. J Agric Food Chem,2021,69(20):5618-5627.
[21] REN Z,XIE Z,CAO D,et al. C-Phycocyanin inhibits hepatic gluco-neogenesis and increases glycogen synthesis via activating Akt and AMPK in insulin resistance hepatocytes[J]. Food Funct,2018,9(5):2829-2839.
[22] HE J,ZHANG P,SHEN L,et al. Short-chain fatty acids and their association with signalling pathways in inflammation,glucose and lipid metabolism [J]. Int J Mol Sci,2020,21(17):6356.
[23] SAKAKIBARA S,YAMAUCHI T,OSHIMA Y,et al. Acetic acid ac-tivates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice[J]. Biochem Biophys Res Commun,2006,344(2):597-604.
[24] FANG K,WU F,CHEN G,et al. Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells [J]. BMC Comple-ment Altern Med,2019,19(1):255.
[25] LALLY J S V,GHOSHAL S,DEPERALTA D K,et al. Inhibition of acetyl-COA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma [J]. Cell Metab,2019,29(1):174-182.e175.
[26] PANG Y,XU X,XIANG X,et al. High fat activates O-GlcNAcyla-tion and affects AMPK/ACC pathway to regulate lipid metabolism[J]. Nutrients,2021,13(6):1740.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金面上项目(81670731,81870547
作者简介:孙亚朝(1989-),男,主管技师,硕士在读,研究方向:免疫学;
通信作者:牛文彦,E-mail:wniu@tmu.edu.cn。
更新日期/Last Update: 2023-04-30