中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

胃促生长素和肥胖抑制素在非酒精性脂肪性肝病发展中的作用

高冰冰 郭宏华

引用本文:
Citation:

胃促生长素和肥胖抑制素在非酒精性脂肪性肝病发展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.05.052
利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:高冰冰负责资料收集与分析,撰写、修改论文并最后定稿;郭宏华负责课题设计,指导撰写论文。
详细信息
    作者简介:

    高冰冰(1993—),女,主要从事消化系统疾病的发病机制及临床诊治研究

    通信作者:

    郭宏华,soyguo@163.com

  • 中图分类号: R725.7

Role of ghrelin and obestatin in the progression of nonalcoholic fatty liver disease

  • 摘要: 非酒精性脂肪性肝病(NAFLD)是一种多因素所致的疾病,可进展为肝硬化和肝细胞癌。目前,NAFLD的发病机制尚未完全清楚,并且临床上尚未有有效的治疗药物,寻找副作用少、能够有效延缓或者逆转疾病进展的新药尤为重要。研究表明,由胃组织产生的相关激素在参与维持能量稳态和肥胖的调节中具有多种效应,胃底基因中的炎症相关基因表达水平与肝病的严重程度一致,因此,有理由认为胃是导致NAFLD的重要参与者之一。总结了胃产生的胃促生长素和肥胖抑制素在NAFLD发展中的作用,为NAFLD的发病机制提供了一个新的观点,并为其治疗提供了一个新的方向。

     

  • [1] ESLAM M, NEWSOME PN, SARIN SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement[J]. J Hepatol. 2020, 73(1): 202-209. DOI: 10.1016/j.jhep.2020.03.039.
    [2] 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.
    [3] ZHOU F, ZHOU J, WANG W, et al. Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: A systematic review and Meta-analysis[J]. Hepatology, 2019, 70(4): 1119-1133. DOI: 10.1002/hep.30702.
    [4] ZHOU Q, SU J, JI MY. Research on self-management status quo and influencing factors of patients with non-alcoholic fatty liver disease[J]. China Med Herald, 2020, 17(6): 26-29. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202006008.htm

    周谦, 苏娟, 季梦遥. 非酒精性脂肪性肝病的治疗研究进展[J]. 中国医药导报, 2020, 17(6): 26-29. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202006008.htm
    [5] LONARDO A, NASCIMBENI F, MANTOVANI A, et al. Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?[J]. J Hepatol, 2018, 68(2): 335-352. DOI: 10.1016/j.jhep.2017.09.021.
    [6] WANG YH, GAO Y. Research progress in diagnosis and treatment of non-alcoholic fatty liver disease combinated with type 2 diabetes mellitus[J]. J Jilin Univ(Med Edit), 2020, 46(6): 1324-1331. DOI: 10.13481/j.1671-587x.20200634.

    王雨涵, 高影. 非酒精性脂肪性肝病并发2型糖尿病诊断和治疗的研究进展[J]. 吉林大学学报(医学版), 2020, 46(6): 1324-1331. DOI: 10.13481/j.1671-587x.20200634.
    [7] HANG SX, SHEN HY, CHEN M. Correlation of serum SHGB levels with insulin sensitivity, lipid metabolism, oxidative stress in patients with nonalcoholic fatty liver disease[J]. J Clin Exp Med, 2019, 18(1): 82-85. DOI: 10.3969/j.issn.1671-4695.2019.01.024.

    杭双熊, 申红玉, 陈敏. 非酒精性脂肪性肝病患者血清SHGB含量与胰岛素敏感性、脂代谢、氧化应激的相关性[J]. 临床和实验医学杂志, 2019, 18(1): 82-85. DOI: 10.3969/j.issn.1671-4695.2019.01.024.
    [8] DAY CP, JAMES OF. Steatohepatitis: A tale of two "hits"?[J]. Gastroenterology, 1998, 114(4): 842-845. DOI: 10.1016/s0016-5085(98)70599-2.
    [9] BUZZETTI E, PINZANI M, TSOCHATZIS EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)[J]. Metabolism, 2016, 65(8): 1038-1048. DOI: 10.1016/j.metabol.2015.12.012.
    [10] BIRERDINC A, STODDARD S, YOUNOSSI ZM. The stomach as an endocrine organ: Expression of key modulatory genes and their contribution to obesity and non-alcoholic fatty liver disease (NAFLD)[J]. Curr Gastroenterol Rep, 2018, 20(6): 24. DOI: 10.1007/s11894-018-0629-6.
    [11] EZQUERRO S, MÉNDEZ-GIMÉNEZ L, BECERRIL S, et al. Acylated and desacyl ghrelin are associated with hepatic lipogenesis, β-oxidation and autophagy: Role in NAFLD amelioration after sleeve gastrectomy in obese rats[J]. Sci Rep, 2016, 6: 39942. DOI: 10.1038/srep39942.
    [12] KOJIMA M, HOSODA H, DATE Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach[J]. Nature, 1999, 402(6762): 656-660. DOI: 10.1038/45230.
    [13] STOJSAVLJEVIĆ S, GOMERČIĆ PALČIĆ M, VIROVIĆ JUKIĆ L, et al. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2014, 20(48): 18070-18091. DOI: 10.3748/wjg.v20.i48.18070.
    [14] KOJIMA M, KANGAWA K. Ghrelin: Structure and function[J]. Physiol Rev, 2005, 85(2): 495-522. DOI: 10.1152/physrev.00012.2004.
    [15] MVLLER TD, NOGUEIRAS R, ANDERMANN ML, et al. Ghrelin[J]. Mol Metab, 2015, 4(6): 437-460. DOI: 10.1016/j.molmet.2015.03.005.
    [16] EZQUERRO S, FRVHBECK G, RODRÍGUEZ A. Ghrelin and autophagy[J]. Curr Opin Clin Nutr Metab Care, 2017, 20(5): 402-408. DOI: 10.1097/MCO.0000000000000390.
    [17] MARCHESINI G, PAGOTTO U, BUGIANESI E, et al. Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance[J]. J Clin Endocrinol Metab, 2003, 88(12): 5674-5679. DOI: 10.1210/jc.2003-031094.
    [18] LI Y, HAI J, LI L, et al. Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non- alcoholic fatty liver disease development[J]. Endocrine, 2013, 43(2): 376-386. DOI: 10.1007/s12020-012-9761-5.
    [19] PORTEIRO B, DÍAZ-RUÍZ A, MARTÍNEZ G, et al. Ghrelin requires p53 to stimulate lipid storage in fat and liver[J]. Endocrinology, 2013, 154(10): 3671-3679. DOI: 10.1210/en.2013-1176.
    [20] KHALEEL EF, ABDEL-ALEEM GA. Obestatin protects and reverses nonalcoholic fatty liver disease and its associated insulin resistance in rats via inhibition of food intake, enhancing hepatic adiponectin signaling, and blocking ghrelin acylation[J]. Arch Physiol Biochem, 2019, 125(1): 64-78. DOI: 10.1080/13813455.2018.1437638.
    [21] MAO YQ, FAN XM. Research advances of ghrelin on nonalcoholic fatty liver disease(NAFLD)[J]. Fudan Univ J Med Sci, 2014, 41(2): 264-268. DOI: 10.3969/j.issn.1672-8467. 2014. 02. 022.

    毛雨晴, 樊晓明. 饥饿素(ghrelin)在非酒精性脂肪肝病(NAFLD)中的研究进展[J]. 复旦学报(医学版), 2014, 41(2): 264-268. DOI: 10.3969/j.issn.1672-8467. 2014. 02. 022.
    [22] CHURM R, DAVIES JS, STEPHENS JW, et al. Ghrelin function in human obesity and type 2 diabetes: A concise review[J]. Obes Rev, 2017, 18(2): 140-148. DOI: 10.1111/obr.12474.
    [23] LI Z, XU G, QIN Y, et al. Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPARγ signaling pathway[J]. Proc Natl Acad Sci U S A, 2014, 111(36): 13163-13168. DOI: 10.1073/pnas.1411571111.
    [24] FERRÉ P. The biology of peroxisome proliferator-activated receptors: Relationship with lipid metabolism and insulin sensitivity[J]. Diabetes, 2004, 53 (Suppl 1): s43-s50. DOI: 10.2337/diabetes.53.2007.s43.
    [25] QUIÑONES M, AL-MASSADI O, FOLGUEIRA C, et al. p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1[J]. Nat Commun, 2018, 9(1): 3432. DOI: 10.1038/s41467-018-05711-6.
    [26] GUO ZH, ZANG P, SHAO JQ. Ghrelin with glucose, lipid metabolism, energy balance and obesity[J]. Chin J Diab, 2019, 27(4): 316-320. DOI: 10.3969/j.issn.1006-6187.2019.04.016.

    郭展宏, 臧璞, 邵加庆. 胃饥饿素与糖脂代谢、能量平衡及肥胖的关系[J]. 中国糖尿病杂志, 2019, 27(4): 316-320. DOI: 10.3969/j.issn.1006-6187.2019.04.016.
    [27] GUILLORY B, JAWANMARDI N, IAKOVA P, et al. Ghrelin deletion protects against age-associated hepatic steatosis by downregulating the C/EBPα-p300/DGAT1 pathway[J]. Aging Cell, 2018, 17(1): e12688. DOI: 10.1111/acel.12688.
    [28] BARAZZONI R, SEMOLIC A, CATTIN MR, et al. Acylated ghrelin limits fat accumulation and improves redox state and inflammation markers in the liver of high-fat-fed rats[J]. Obesity (Silver Spring), 2014, 22(1): 170-177. DOI: 10.1002/oby.20454.
    [29] EZQUERRO S, FRVHBECK G, RODRÍGUEZ A. Ghrelin and autophagy[J]. Curr Opin Clin Nutr Metab Care, 2017, 20(5): 402-408. DOI: 10.1097/MCO.0000000000000390.
    [30] MAO Y, CHENG J, YU F, et al. Ghrelin attenuated lipotoxicity via autophagy induction and nuclear factor-κB inhibition[J]. Cell Physiol Biochem, 2015, 37(2): 563-576. DOI: 10.1159/000430377.
    [31] EZQUERRO S, MOCHA F, FRVHBECK G, et al. Ghrelin reduces TNF-α-induced human hepatocyte apoptosis, autophagy, and pyroptosis: Role in obesity-associated NAFLD[J]. J Clin Endocrinol Metab, 2019, 104(1): 21-37. DOI: 10.1210/jc.2018-01171.
    [32] IWASAKI T, YONEDA M, NAKAJIMA A, et al. Serum butyrylcholinesterase is strongly associated with adiposity, the serum lipid profile and insulin resistance[J]. Intern Med, 2007, 46(19): 1633-1639. DOI: 10.2169/internalmedicine.46.0049.
    [33] GE X, YANG H, BEDNAREK MA, et al. LEAP2 Is an endogenous antagonist of the ghrelin receptor[J]. Cell Metab, 2018, 27(2): 461-469. e6. DOI: 10.1016/j.cmet.2017.10.016.
    [34] CHEN VP, GAO Y, GENG L, et al. Butyrylcholinesterase deficiency promotes adipose tissue growth and hepatic lipid accumulation in male mice on high-fat diet[J]. Endocrinology, 2016, 157(8): 3086-3095. DOI: 10.1210/en.2016-1166.
    [35] XING YX, YANG L, KUANG HY, et al. Function of obestatin in the digestive system[J]. Nutrition. 2017, 34: 21-28. DOI: 10.1016/j.nut.2016.08.009.
    [36] TROVATO L, GALLO D, SETTANNI F, et al. Obestatin: Is it really doing something?[J]. Front Horm Res, 2014, 42: 175-185. DOI: 10.1159/000358346.
    [37] ZHANG JV, REN PG, AVSIAN-KRETCHMER O, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake[J]. Science, 2005, 310(5750): 996-999. DOI: 10.1126/science.1117255.
    [38] XING YX, YANG L, KUANG HY, et al. Function of obestatin in the digestive system[J]. Nutrition, 2017, 34: 21-28. DOI: 10.1016/j.nut.2016.08.009.
    [39] SEIM I, WALPOLE C, AMORIM L, et al. The expanding roles of the ghrelin-gene derived peptide obestatin in health and disease[J]. Mol Cell Endocrinol, 2011, 340(1): 111-117. DOI: 10.1016/j.mce.2011.03.018.
    [40] CHARTREL N, ALVEAR-PEREZ R, LEPRINCE J, et al. Comment on "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake"[J]. Science, 2007, 315(5813): 766; author reply 766. DOI: 10.1126/science.1135047.
    [41] ESTEP M, ABAWI M, JARRAR M, et al. Association of obestatin, ghrelin, and inflammatory cytokines in obese patients with non-alcoholic fatty liver disease[J]. Obes Surg, 2011, 21(11): 1750-1757. DOI: 10.1007/s11695-011-0475-1.
    [42] GESMUNDO I, GALLO D, FAVARO E, et al. Obestatin: A new metabolic player in the pancreas and white adipose tissue[J]. IUBMB Life, 2013, 65(12): 976-982. DOI: 10.1002/iub.1226.
    [43] GREEN BD, GRIEVE DJ. Biochemical properties and biological actions of obestatin and its relevence in type 2 diabetes[J]. Peptides, 2018, 100: 249-259. DOI: 10.1016/j.peptides.2017.12.006.
    [44] COWAN E, BURCH KJ, GREEN BD, et al. Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes[J]. Br J Pharmacol, 2016, 173(14): 2165-2181. DOI: 10.1111/bph.13502.
    [45] PRADHAN G, WU CS, HAN LEE J, et al. Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R[J]. Sci Rep, 2017, 7(1): 979. DOI: 10.1038/s41598-017-00888-0.
    [46] SUO YH, LIU JC. Research advances in the treatment of nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2018, 34(10): 2232-2236. DOI: 10.3969/j.issn.1001-5256.2018.10.038.

    索宇鸿, 刘近春. 非酒精性脂肪性肝病的治疗进展[J]. 临床肝胆病杂志, 2018, 34(10): 2232-2236. DOI: 10.3969/j.issn.1001-5256.2018.10.038.
    [47] KANAT BH, AYTEN R, AYDIN S, et al. Significance of appetite hormone ghrelin and obestatin levels in the assessment of the severity of acute pancreatitis[J]. Turk J Gastroenterol, 2014, 25(3): 309-313. DOI: 10.5152/tjg.2014.4081.
  • 加载中
计量
  • 文章访问数:  402
  • HTML全文浏览量:  138
  • PDF下载量:  31
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-09-23
  • 录用日期:  2020-10-23
  • 出版日期:  2021-05-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回