果糖引起的非酒精性脂肪性肝病相关机制的研究进展

陈晔; 吴锦露; 潘文婷; 李海鹰

doi:10.3969/j.issn.1001-5256.2017.12.044

果糖引起的非酒精性脂肪性肝病相关机制的研究进展

DOI: 10.3969/j.issn.1001-5256.2017.12.044

1. 温州医科大学附属第一医院心血管内科
2. 温州医科大学附属第一医院感染内科
3. 温州医科大学第一临床医学院

基金项目:

浙江省自然科学基金(LY14H020007)；

详细信息

中图分类号: R575.5
计量
- 文章访问数: 1410
- HTML全文浏览量: 19
- PDF下载量: 375
- 被引次数: 0
出版历程
- 收稿日期: 2017-07-13
- 出版日期: 2017-12-20

Research advances in the mechanism of fructose-induced nonalcoholic fatty liver disease

Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University

Research funding:

摘要

摘要: 近年来非酒精性脂肪性肝病的发病率在发达国家及发展中国家均呈上升趋势,这与果糖消耗量增加有着重要的联系。介绍了慢性持续性果糖摄入能够显著促进肝脏脂肪从头合成,引起肝脏ATP消耗及肝细胞再生抑制,并导致肝细胞内质网应激和活性氧化物质产生增加,最终出现非酒精性脂肪性肝病。认为研究果糖引发非酒精性脂肪性肝病的具体机制、破坏肝脏中的果糖代谢可为非酒精性脂肪性肝病的治疗提供新的选择。
- 非酒精性脂肪性肝炎 /
- 果糖 /
- 综述
Abstract: In recent years, the incidence rate of nonalcoholic fatty liver disease ( NAFLD) tends to increase in both developed and developing countries, which is associated with an increase in fructose consumption. This article points out that chronic persistent fructose intake can significantly promote de novo lipogenesis ( DNL) in the liver and induce ATP depletion and inhibition of hepatocyte regeneration, which further causes endoplasmic reticulum stress and increased production of reactive oxygen species in the liver and finally leads to the development of NAFLD. It is believed that detailed mechanism of fructose-induced NAFLD and disruption of fructose metabolism in the liver may provide new therapeutic strategies for NAFLD.
- nonalcoholic fatty liver disease /
- fructose /
- review

HTML全文

参考文献(30)

[1]WANG H, TENG T, WANG L, et al.Research advances in the pathogenesis of nonalcoholic fatty liver disease[J].J Clin Hepatol, 2017, 33 (4) :769-773. (in Chinese) 王虎, 滕田, 王莉, 等.非酒精性脂肪性肝病发病机制的研究进展[J].临床肝胆病杂志, 2017, 33 (4) :769-773.

[2]CALDWELL S, ARGO C.The natural history of non-alcoholic fatty liver disease[J].Dig Dis, 2010, 28 (1) :162-168.

[3]WONG VW, VERGNIOL J, WONG GL, et al.Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease[J].Hepatology, 2010, 51 (2) :454-462.

[4]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.

[5]LIM JS, MIETUS-SNYDER M, VALENTE A, et al.The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome[J].Nat Rev Gastroenterol Hepatol, 2010, 7 (5) :251-264.

[6]BASARANOGLU M, BASARANOGLU G, SABUNCU T, et al.Fructose as a key player in the development of fatty liver disease[J].World J Gastroenterol, 2013, 19 (8) :1166-1172.

[7]SAKAR Y, NAZARET C, LETTRON P, et al.Positive regulatory control loop between gut leptin and intestinal glut2/glut5 transporters links to hepatic metabolic functions in rodents[J].Plos One, 2009, 4 (11) :e7935.

[8]LYSSIOTIS CA, CANTLEY LC.Metabolic syndrome:fstands for fructose and fat[J].Nature, 2013, 502 (7470) :181-182.

[9]WANG Q, LI S, JIANG L, et al.Deficiency in hepatic ATP-citrate lyase affects VLDL-triglyceride mobilization and liver fatty acid composition in mice[J].J Lipid Res, 2010, 51 (9) :2516-2526.

[10]SOFTIC S, COHEN DE, KAHN CR.Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease[J].Dig Dis Sci, 2016, 61 (5) :1282-1293.

[11]HIGUCHI N, KATO M, SHUNDO Y, et al.Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease[J].Hepatol Res, 2008, 38 (11) :1122-1129.

[12]HORTON JD, BASHMAKOV Y, SHIMOMURA I, et al.Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice[J].Proc Natl Acad Sci U S A, 1998, 95 (11) :5987-5992.

[13]SOFTIC S, KIRBY M, BERGER NG, et al.Insulin concentration modulates hepatic lipid accumulation in mice in part via transcriptional regulation of fatty acid transport proteins[J].PLo S One, 2012, 7 (6) :e38952.

[14]HAAS JT, MIAO J, CHANDA D, et al.Hepatic insulin signaling is required for obesity-dependent expression of srebp-1c mrna but not for feeding-dependent expression[J].Cell Metab, 2012, 15 (6) :873-884.

[15]JURCZAK MJ, LEE AH, JORNAYVAZ FR, et al.Dissociation of inositol-requiring enzyme (ire1 alpha) -mediated c-jun n-terminal kinase activation from hepatic insulin resistance in conditional x-box-binding protein-1 (xbp1) knock-out mice[J].J Biol Chem, 2012, 287 (4) :2558-2567.

[16]GREGOR MF, YANG L, FABBRINI E, et al.Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss[J].Diabetes, 2009, 58 (3) :693-700.

[17]LEE AH, SCAPA EF, COHEN DE, et al.Regulation of hepatic lipogenesis by the transcription factor XBP1[J].Science, 2008, 320 (5882) :1492-1496.

[18]NAKAGAWA T, HU H, ZHARIKOV S, et al.A causal role for uric acid in fructose-induced metabolic syndrome[J].Am J Physiol Renal Physiol, 2006, 290 (3) :F625-F631.

[19]BOESIGER P, BUCHLI R, MEIER D, et al.Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy[J].Pediatr Res, 1994, 36 (4) :436-440.

[20]SPEICHER T, KHLER UA, CHOUKR A, et al.Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating jnk signaling[J].J Biol Chem, 2012, 287 (3) :1837-1846.

[21]LANASPA MA, SANCHEZ-LOZADA LG, CHOI YJ, et al.Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress:potential role in fructose-dependent and-independent fatty liver[J].J Biol Chem, 2012, 287 (48) :40732-40744.

[22]DAY CP, JAMES OF.Steatohepatitis:a tale of two"hits"?[J].Gastroenterology, 1998, 114 (4) :842-845.

[23]ALWAHSH SM, GEBHARDT R.Dietary fructose as a risk factor for non-alcoholic fatty liver disease (NAFLD) [J].Arch Toxicol, 2017, 91 (4) :1545-1563.

[24]KOHLI R, PAN XM, MALLADI P, et al.Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway[J].J Biol Chem, 2007, 282 (29) :21327-21336.

[25]HAN ML, GONG ZH.Mechanism of action of gut microbiota in hepatobiliary disease[J].J Clin Hepatol, 2017, 33 (2) :384-388. (in Chinese) 韩美林, 龚振华.肠道菌群在肝胆疾病中的作用机制[J].临床肝胆病杂志, 2017, 33 (2) :384-388.

[26]WIGG AJ, ROBERTS-THOMSON IC, DYMOCK RB, et al.The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis[J].Gut, 2001, 48 (2) :206-211.

[27]SPRUSS A, KANURI G, STAHL C, et al.Metformin protects against the development of fructose-induced steatosis in mice:role of the intestinal barrier function[J].Lab Invest, 2012, 92 (7) :1020-1032.

[28]MATAK P, ZUMERLE S, MASTROGIANNAKI M, et al.Copper deficiency leads to anemia, duodenal hypoxia, upregulation of HIF-2alpha and altered expression of iron absorption genes in mice[J].PLo S One, 2013, 8 (3) :e59538.

[29]SONG M, SCHUSCHKE DA, ZHOU Z, et al.High fructose feeding induces copper deficiency in Sprague-Dawley rats:a novel mechanism for obesity related fatty liver[J].J Hepatol, 2012, 56 (2) :433-440.

[30]SONG M, SCHUSCHKE DA, ZHOU Z, et al.Modest fructose beverage intake causes liver injury and fat accumulation in marginal copper deficient rats[J].Obesity (Silver Spring) , 2013, 21 (8) :1669-1675.

施引文献

资源附件(0)

访问统计