[1]吕枭锐 朱惠娟 龚凤英.肝细胞因子与非酒精性脂肪性肝病[J].国际内分泌代谢杂志,2020,40(03):206-210.[doi:10.3760/cma.j.issn.1673-4157.2020.03.014]
　Lyu Xiaorui,Zhu Huijuan,Gong Fengying.Hepatokines and nonalcoholic fatty liver disease[J].International Journal of Endocrinology and Metabolism,2020,40(03):206-210.[doi:10.3760/cma.j.issn.1673-4157.2020.03.014]
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肝细胞因子与非酒精性脂肪性肝病()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
40
期数:
2020年03期
页码:
206-210
栏目:
基础研究
出版日期:
2020-05-20

文章信息/Info

Title:
Hepatokines and nonalcoholic fatty liver disease
作者:
吕枭锐 朱惠娟 龚凤英
中国医学科学院,北京协和医学院,北京协和医院内分泌科,卫生健康委内分泌重点实验室,协和转化医学中心 100730
Author(s):
Lyu Xiaorui;  Zhu Huijuan;  Gong Fengying
Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, The Translational Medicine Center of PUMCH, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
关键词:
肝细胞因子;  非酒精性脂肪性肝病;  肝脂肪变性
Keywords:
Hepatokines;  Nonalcoholic fatty liver disease;  Liver steatosis
DOI:
10.3760/cma.j.issn.1673-4157.2020.03.014
摘要:
非酒精性脂肪性肝病(NAFLD)是目前最常见的慢性肝病,其特点是肝脏内脂肪大量堆积(脂肪变性)。肝细胞因子指由肝脏分泌的具有自分泌、旁分泌或内分泌活性的蛋白质,主要功能为调节脂质和葡萄糖代谢。研究发现,在发生肝脏脂肪变性时,许多肝细胞因子的表达会发生变化,包括成纤维细胞生长因子21、性激素结合球蛋白、adropin、血管生成素样蛋白8、胎球蛋白A、视黄醇结合蛋白4、hepassocin、硒蛋白P和白细胞衍生趋化因子2等,它们抑制或者促进NAFLD的形成,在该过程中发挥重要作用。
Abstract:
Nonalcoholic fatty liver disease(NAFLD), the most common chronic liver disease,is characterized by a large accumulation of fat in the liver. Hepatokines are a kind of proteins secreted by the liver which regulate lipid and glucose metabolism in autocrine, paracrine or endocrine ways. Studies showed that the expression of many hepatokines are changed when hepatic steatosis occurred, including fibroblast growth factor 21, sex hormone-binding globulin, adropin, fetuin A, retinol binding protein 4, angiopoietin-like protein 8, hepassocin and leukocyte cell-derived chemotaxin 2.These hepatokines can inhibit or promote the formation of NAFLD, and therefore play important roles in this process.

参考文献/References:

[1] Caldwell S,Argo C.The natural history of non-alcoholic fatty liver disease[J].Dig Dis,2010,28(1):162-168. DOI:10.1159/000282081.
[2] Vernon G,Baranova A,Younossi ZM.Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults[J].Aliment Pharmacol Ther,2011,34(3):274-285.DOI:10.1111/j.1365-2036.2011.04724.x.
[3] Younossi ZM,Koenig AB,Abdelatif D,et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence,and outcomes[J].Hepatology,2016,64(1):73-84.DOI:10.1002/hep.28431.
[4] Ong JP,Pitts A,Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease[J].J Hepatol,2008,49(4):608-612. DOI:10.1016/j.jhep.2008.06.018.
[5] Takaki A,Kawai D,Yamamoto K.Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholicsteatohepatitis(NASH)[J].Int J Mol Sci,2013,14(10):20704-20728.DOI:10.3390/ijms141020704.
[6] Donnelly KL,Smith CI,Schwarzenberg SJ,et al.Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease[J].J Clin Invest,2005,115(5):1343-1351.DOI:10.1172/JCI23621.
[7] Kawano Y,Cohen DE. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease[J].J Gastroenterol,2013,48(4):434-441. DOI:10.1007/s00535-013-0758-5.
[8] Gentile CL,Pagliassotti MJ.The role of fatty acids in the development and progression of nonalcoholic fatty liver disease[J].J Nutr Biochem,2008,19(9):567-576.DOI:10.1016/j.jnutbio.2007.10.001.
[9] Liu J,Xu Y,Hu Y,et al.The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy[J].Metabolism,2015,64(3):380-390.DOI:10.1016/j.metabol.2014.11.009.
[10] Auberger P,Falquerho L,Contreres JO,et al.Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity[J].Cell,1989,58(4):631-640.DOI:10.1016/0092-8674(89)90098-6.
[11] Stefan N,Häring HU.The role of hepatokines in metabolism[J].Nat Rev Endocrinol,2013,9(3):144-152.DOI:10.1038/nrendo.2012.258.
[12] Fu S,Fan J,Blanco J,et al.Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting[J].PLoS Genet,2012,8(8):e1002902.DOI:10.1371/journal.pgen.1002902.
[13] Kharitonenkov A,Shiyanova TL,Koester A,et al.FGF-21 as a novel metabolic regulator[J].J Clin Invest,2005,115(6):1627-1635.DOI:10.1172/JCI23606.
[14] Woolsey SJ,Beaton MD,Mansell SE,et al.A fibroblast growth factor 21-Pregnane X receptor pathway downregulates hepatic CYP3A4 in nonalcoholic fatty liver disease[J].Mol Pharmacol,2016,90(4):437-446.DOI:10.1124/mol.116.104687.
[15] Alisi A,Ceccarelli S,Panera N,et al. Association between serum atypical fibroblast growth factors 21 and 19 and pediatric nonalcoholic fatty liver disease[J].PLoS One,2013,8(6):e67160.DOI:10.1371/journal.pone.0067160.
[16] Reinehr T,Woelfle J,Wunsch R,et al. Fibroblast growth factor 21(FGF-21)and its relation to obesity,metabolic syndrome, and nonalcoholic fatty liver in children:a longitudinal analysis[J].J Clin Endocrinol Metab,2012,97(6):2143-2150.DOI:10.1210/jc.2012-1221.
[17] Yilmaz Y,Eren F,Yonal O,et al. Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease[J].Eur J Clin Invest,2010,40(10):887-892. DOI:10.1111/j.1365-2362.2010.02338.x.
[18] Zarei M,Barroso E,Palomer X,et al.Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liverdisease[J].Mol Metab,2018,8:117-131.DOI:10.1016/j.molmet.2017.12.008.
[19] Zhu S,Wu Y,Ye X,et al.FGF21 ameliorates nonalcoholic fatty liver disease by inducing autophagy[J].Mol Cell Biochem,2016,420(1-2):107-119.DOI:10.1007/s11010-016-2774-2.
[20] Petra PH.The plasma sex steroid binding protein(SBP or SHBG). A critical review of recent developments on the structure, molecular biology and function[J].J Steroid Biochem Mol Biol,1991,40(4-6):735-753.DOI:10.1016/0960-0760(91)90299-k.
[21] Polyzos SA,Kountouras J,Tsatsoulis A,et al.Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease[J].Hormones(Athens),2013,12(3):405-416.DOI:10.1007/BF03401306.
[22] Hua X,Li M,Pan F,et al.Non-alcoholic fatty liver disease is an influencing factor for the association of SHBG with metabolic syndrome in diabetes patients[J].Sci Rep,2017,7(1):14532.DOI:10.1038/s41598-017-15232-9.
[23] Lazo M,Zeb I,Nasir K,et al. Association between endogenous sex hormones and liver fat in a multiethnic study of atherosclerosis[J].Clin Gastroenterol Hepatol,2015,13(9):1686-1693.e2.DOI:10.1016/j.cgh.2014.12.033.
[24] Bonnet F,Velayoudom Cephise FL,Gautier A,et al.Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features[J].Clin Endocrinol(Oxf),2013,79(4):517-522.DOI:10.1111/cen.12089.
[25] Shin JY,Kim SK,Lee MY,et al.Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fattyliver disease in people with type 2 diabetes[J].Diabetes Res Clin Pract,2011,94(1):156-162.DOI:10.1016/j.diabres.2011.07.029.
[26] Saez-Lopez C,Barbosa-Desongles A,Hernandez C,et al.Sex hormone-binding globulin reduction in metabolic disorders may play a role in NAFLD development[J].Endocrinology,2017,158(3):545-559.DOI:10.1210/en.2016-1668.
[27] Kumar KG,Trevaskis JL,Lam DD,et al.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism[J].Cell Metab,2008,8(6):468-481.DOI:10.1016/j.cmet.2008.10.011.
[28] Sayn O,Tokgöz Y,Arslan N. Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease[J].J Pediatr Endocrinol Metab,2014,27(5-6):479-484.DOI:10.1515/jpem-2013-0296.
[29] Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels[J].Biochem Biophys Res Commun,2012,424(4):786-792. DOI:10.1016/j.bbrc.2012.07.038.
[30] Lee YH,Lee SG,Lee CJ,et al. Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease: animal and human studies[J].Sci Rep,2016,6:24013. DOI:10.1038/srep24013.
[31] Hong BS,Liu J,Zheng J,et al. Angiopoietin-like protein 8/betatrophin correlates with hepatocellular lipid content independent of insulin resistance in non-alcoholic fatty liver disease patients[J].J Diabetes Investig,2018,9(4):952-958. DOI:10.1111/jdi.12792.
[32] Vatner DF,Goedeke L,Camporez JG,et al. Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents[J].Diabetologia,2018,61(6):1435-1446.DOI:10.1007/s00125-018-4579-1.
[33] García-Monzón C,Petrov PD,Rey E,et al.Angiopoietin-like protein 8 is a novel vitamin D receptor target gene involved in nonalcoholic fatty liver pathogenesis[J].Am J Pathol,2018,188(12):2800-2810. DOI:10.1016/j.ajpath.2018.07.028.
[34] Denecke B,Gräber S,Schäfer C,et al.Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A[J].Biochem J,2003,376(Pt 1):135-145. DOI:10.1042/BJ20030676.
[35] von Loeffelholz C,Horn P,Birkenfeld AL,et al.Fetuin A is a predictor of liver fat in preoperative patients with nonalcoholic fatty liver disease[J].J Invest Surg,2016,29(5):266-274. DOI:10.3109/08941939.2016.1149640.
[36] Huang Y,Huang X,Ding L,et al. Serum fetuin-a associated with fatty liver index, early indicator of nonalcoholic fatty liver disease:a strobe-compliant article[J].Medicine(Baltimore),2015,94(39):e1517.DOI:10.1097/MD.0000000000001517.
[37] Haukeland JW,Dahl TB,Yndestad A,et al.Fetuin A in nonalcoholic fatty liver disease:in vivo and in vitro studies[J].Eur J Endocrinol,2012,166(3):503-510.DOI:10.1530/EJE-11-0864.
[38] Christou GA,Tselepis AD,Kiortsis DN. The metabolic role of retinol binding protein 4:an update[J].Horm Metab Res,2012,44(1):6-14. DOI:10.1055/s-0031-1295491.
[39] Cengiz C,Ardicoglu Y,Bulut S,et al.Serum retinol-binding protein 4 in patients with nonalcoholic fatty liver disease: does it have a significant impact on pathogenesis?[J].Eur J Gastroenterol Hepatol,2010,22(7):813-819. DOI:10.1097/MEG.0b013e32833283cb.
[40] Wang X,Chen X,Zhang H,et al. Circulating retinol-binding protein 4 is associated with the development and regression of non-alcoholic fatty liver disease[J].Diabetes Metab,2019.S1262-3636(19)30069-2.DOI:10.1016/j.diabet.2019.04.009.
[41] Zhou Z,Chen H,Ju H,et al. Circulating retinol binding protein 4 levels in nonalcoholic fatty liver disease: a systematic review and meta-analysis[J].Lipids Health Dis,2017,16(1):180.DOI:10.1186/s12944-017-0566-7.
[42] Yan H,Chang X,Xia M,et al.Serum retinol binding protein 4 is negatively related to beta cell function in Chinese women with non-alcoholic fatty liver disease:a cross-sectional study[J].Lipids Health Dis,2013,12:157. DOI:10.1186/1476-511X-12-157.
[43] Chang X,Yan H,Bian H,et al. Serum retinol binding protein 4 is associated with visceral fat in human with nonalcoholic fatty liver disease without known diabetes:a cross-sectional study[J].Lipids Health Dis,2015,14:28.DOI:10.1186/s12944-015-0033-2.
[44] Schina M,Koskinas J,Tiniakos D,et al.Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease[J].Hepatol Res,2009,39(10):972-978. DOI:10.1111/j.1872-034X.2009.00534.x.
[45] Hara H,Uchida S,Yoshimura H,et al.Isolation and characterization of a novel liver-specific gene, hepassocin, upregulated during liver regeneration[J].Biochim Biophys Acta,2000,1492(1):31-44. DOI:10.1016/s0167-4781(00)00056-7.
[46] Abdelmoemen G,Khodeir SA,Zaki AN,et al.Overexpression of hepassocin in diabetic patients with nonalcoholic fatty liver disease may facilitate increased hepatic lipid accumulation[J].Endocr Metab Immune Disord Drug Targets,2019,19(2):185-188.DOI:10.2174/1871530318666180716100543.
[47] Wu HT,Lu FH,Ou HY,et al.The role of hepassocin in the development of non-alcoholic fatty liver disease[J].J Hepatol,2013,59(5):1065-1072.DOI:10.1016/j.jhep.2013.06.004.
[48] Burk RF,Hill KE.Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis[J].Annu Rev Nutr,2005,25:215-235.DOI:10.1146/annurev.nutr.24.012003.132120.
[49] Cetindagˇ I,Kara M,Tanoglu A,et al.Evaluation of endothelial dysfunction in patients with nonalcoholic fatty liver disease: association of selenoprotein P with carotid intima-media thickness and endothelium-dependent vasodilation[J].Clin Res Hepatol Gastroenterol,2017,41(5):516-524.DOI:10.1016/j.clinre.2017.01.005.
[50] Lee SM,Kwak SH,Koo JN,et al.Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus[J].Diabetologia,2019,62(2):238-248.DOI:10.1007/s00125-018-4779-8.
[51] Choi HY,Hwang SY,Lee CH,et al.Increased selenoprotein p levels in subjects with visceral obesity and nonalcoholic fatty liver disease[J].Diabetes Metab J,2013,37(1):63-71. DOI:10.4093/dmj.2013.37.1.63.
[52] Yamagoe S,Yamakawa Y,Matsuo Y,et al. Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2[J].Immunol Lett,1996,52(1):9-13.DOI:10.1016/0165-2478(96)02572-2.
[53] Yoo HJ,Hwang SY,Choi JH,et al. Association of leukocyte cell-derived chemotaxin 2(LECT2)with NAFLD, metabolic syndrome, and atherosclerosis[J].PLoS One,2017,12(4):e0174717.DOI:10.1371/journal.pone.0174717.
[54] Chikamoto K,Misu H,Takayama H,et al.Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice[J].Biochem Biophys Res Commun,2016,478(3):1310-1316.DOI:10.1016/j.bbrc.2016.08.117.

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备注/Memo

备注/Memo:
通信作者:龚凤英,Email:fygong@sina.com
基金项目:北京市自然科学基金(7182130,7082079); 国家自然科学基金(81370898,30771026,30540036); 人社部留学人员科技活动项目择优资助经费(启动类); 国家临床重点专科建设项目单位(WBYZ2011-873)
Corresponding author: Gong Fengying, Email:fygong@sina.com
Fund program:Natural Science Foundation of Beijing of China(7182130, 7082079); National Natural Science Foundation of China(81370898, 30771026, 30540036); Scientific Research Foundation for the Selected Returned Overseas Chinese Scholars, Ministry of Human Resources and Social Security of China(Start-up); The National Key Program of Clinical Science(WBYZ2011-873)
更新日期/Last Update: 2020-05-20