The mechanisms and impacts of obesity on the development of liver cancer
-
摘要: 肥胖除了与代谢相关性疾病有关外,还与多种肿瘤的发生发展有着紧密关系。归纳了肥胖对肝癌发生发展影响的几种作用机制,包括:瘦素、胰岛素样生长因子1、IL-6、TNFα、脂联素等脂肪细胞因子,胰岛素,胰岛素抵抗,氧化应激反应,肠道微生态紊乱,以及含patatin样磷脂酶域3、miRNA、TM6SF2、和JAZF1等基因方面的调节,对其作用机制的研究进展加以综述,以期对肝癌的预防和治疗起到积极的指导作用。Abstract: Obesity has become a severe public health issue. Studies have shown that obesity is closely associated with metabolic disease and the development and progression of various tumors. This article summarizes the obesity-related factors in the development and progression of liver cancer, including adipokines ( such as leptin, insulin like growth factor-1, interleukin-6, tumor necrosis factor-α, and adiponectin) , insulin, insulin resistance, oxidative stress response, intestinal microecological disorders, and regulations of PNPLA3, miRNA, TM6 SF2, and JAZF1 genes. This article reviews the research advances in these mechanisms, in order to provide guidance for the prevention and treatment of liver cancer.
-
Key words:
- obesity /
- liver neoplasms /
- review
-
[]参考文献[1]CHEN YZ, LIU L, FU XL, et al.Knowledge mapping analysis of the relationship between obesity and cancer[J].Chin J Dis Control Prevent, 2016, 20 (6) :604-608. (in Chinese) 陈燕子, 刘莉, 付晓丽, 等.肥胖与癌症的关系的知识图谱分析[J].中华疾病控制杂志, 2016, 20 (6) :604-608.[2]WONG RJ, CHEUNG R, AHMED A.Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S[J].Hepatology, 2014, 59 (6) :2188.[3]WONG RJ, AGUILAR M, CHEUNG R, et al.Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States[J].Gastroenterology, 2015, 148 (3) :547.[4]SIEGEL AB, LIM EA, WANG S, et al.Diabetes, body mass index, and outcomes in hepatocellular carcinoma patients undergoing liver transplantation[J].Transplantation, 2011, 94 (5) :539.[5]OHKI T, TATEISHI R, SHIINA S, et al.Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH[J].Gut, 2009, 58 (6) :839-844.[6]MOLLER H, MELLEMGAARD A, LINDVIG K, et al.Obesity and cancer risk:a Danish record-linkage study[J].Eur J Cancer, 1994, 30A (3) :344.[7]SAMANIC C, CHOW WH, GRIDLEY G, et al.Relation of body mass index to cancer risk in 362, 552 swedish men[J].Cancer Causes Control, 2006, 17 (7) :901-909.[8]SCHLESINGER S, ALEKSANDROVA K, PISCHON T, et al.Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort[J].Int J Cancer, 2013, 132 (3) :645-657.[9]NAIR S, MASON A, EASON J, et al.Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis[J].Hepatology, 2002, 36 (1) :150-155. [10]YI C, WANG X, WANG J, et al.Excess body weight and the risk of primary liver cancer:an updated meta-analysis of prospective studies[J].Eur J Cancer, 2012, 48 (14) :2137. [11]RIBATTI D, BELLONI AS, NICO B, et al.Leptin-leptin receptor are involved in angiogenesis in human hepatocellular carcinoma[J].Peptides, 2008, 29 (9) :1596-1602. [12]DAI K, TIAN DY.Leptin facilitates the proliferation activity of hepatoma cells via regulating cell cycle proteins[J].J Med Postgrad, 2007, 20 (4) :339-342. (in Chinese) 戴锴, 田德英.瘦素通过调控细胞周期蛋白促进人肝癌细胞增殖[J].医学研究生学报, 2007, 20 (4) :339-342. [13]YAO M, YAN XD, WANG L, et al.Down-regulating insulinlike growth factor-1 receptor gene transcription on effect of hepatoma growth inhibition[J].Chin J Cancer Prev Treat, 2015, 22 (19) :1528-1533. (in Chinese) 姚敏, 严晓娣, 王理, 等.干扰IGF-1R基因表达对肝癌细胞裸鼠移植瘤生长影响研究[J].中华肿瘤防治杂志, 2015, 22 (19) :1528-1533. [14]PARK EJ, LEE JH, YU GY, et al.Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6and TNF expression.[J].Cell, 2010, 140 (2) :197-208. [15]ALI KAMKAR MM, AHMAD R, ALSMADI O, et al.Insight into the impact of diabetes mellitus on the increased risk of hepatocellular carcinoma:mini-review[J].J Diabetes Metab Disord, 2014, 13:57. [16]BARB D, PAZAITOUPANAYIOTOU K, MANTZOROS CS.Adiponectin:a link between obesity and cancer[J].Expert Opinion on Investigational Drugs, 2006, 15 (8) :917-931. [17]ZHOU J, LEI W, SHEN L, et al.Expression and significance of leptin and leptin receptor in hepatocellular carcinoma cells[J].Wuhan Univ Med J, 2009, 30 (3) :376-378. (in Chinese) 周晶, 雷伟, 沈磊, 等.瘦素及其受体蛋白在肝癌细胞中的表达及意义[J].武汉大学学报医学版, 2009, 30 (3) :376-378. [18]LEROITH D, HELMAN AL.The new kid on the block (ade) of the IGF-1 receptor[J].Cancer Cell, 2004, 5 (3) :201-202. [19]YOU M, CONSIDINE RV, LEONE TC, et al.Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice[J].Hepatology, 2005, 42 (3) :568-577. [20]SAXENA NK, FU PP, NAGALINGAM A, et al.Adiponectin modulates C-jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma[J].Gastroenterology, 2010, 139 (5) :1-5. [21]DALAMAGA M, DIAKOPOULOS KN, MANTZOROS CS.The role of adiponectin in cancer:a review of current evidence[J].Endocrine Reviews, 2012, 33 (4) :547-594. [22]WEBER MM, FOTTNER C, LIU SB, et al.Overexpression of the insulin-like growth factor I receptor in human colon carcinomas[J].Cancer, 2002, 95 (10) :2086-2095. [23]KIM SH, REAVEN G.Obesity and insulin resistance:an ongoing saga[J].Diabetes, 2010, 59 (9) :2105-2106. [24]BARTH RJ.Insulin resistance, obesity and the metabolic syndrome[J].S D Med, 2011, Spec No:22-27. [25]AHMED M.Non-alcoholic fatty liver disease in 2015[J].World J Hepatol, 2015, 7 (11) :1450-1459. [26]Group of Fatty Liver and Alcoholic liver Disease, Society of Hepatology, Chinese Medical Association.Guideline for management of non-alcoholic fatty liver diseases[J].J Clin Hepatol, 2010, 26 (2) :120-124. (in Chinese) 中华医学会肝病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南[J].临床肝胆病杂志, 2010, 26 (2) :120-124. [27]LI LP.Nonalcoholic fatty liver disease and hepatocellular carcinoma[J].J Clin Hepatol, 2016, 32 (3) :432-436. (in Chinese) 李良平.非酒精性脂肪性肝病与肝细胞癌[J].临床肝胆病杂志, 2016, 32 (3) :432-436. [28]WENSHENG L, BAKER SS, BAKER RD, et al.Antioxidant mechanisms in nonalcoholic fatty liver disease[J].Current Drug Targets, 2015, 16 (12) :1301-1314. [29]XIAO L, YANG L.Gut microbiota and nonalcoholic fatty liver disease[J].J Clin Hepatol, 2017, 33 (4) :774-779. (in Chinese) 肖丽, 杨玲.肠道菌群与非酒精性脂肪性肝病的关系[J].临床肝胆病杂志, 2017, 33 (4) :774-779. [30]WANG XY, LI YL.Progress in understanding association of PNPLA3 I148M (rs738409) single nucleotide polymorphism with hepatocellular carcinoma and hepatic cirrhosis[J].World Chin JDig, 2014, 22 (29) :4430-4436. (in Chinese) 王心怡, 李异玲.PNPLA3 I148M (rs738409) SNP与肝硬化及肝细胞癌关系的研究进展[J].世界华人消化杂志, 2014, 22 (29) :4430-4436. [31]XU JING, XIN YN, XUAN SY.Polymorphisms in PNPLA3 gene is associated with non-alcoholic fatty liver disease[J].J Clin Hepatol, 2012, 28 (4) :316-320. (in Chinese) 徐静, 辛永宁, 宣世英.PNPLA3基因多态性与非酒精性脂肪性肝病关系的研究进展[J].临床肝胆病杂志, 2012, 28 (4) :316-320. [32] XU J, XIN YN, LYU WH, et al.Polymorphism rs738409 in PNPLA3 is associated with inherited susceptibility to non-alcoholic fatty liver disease[J].Chin J Hepatol, 2013, 21 (8) :619-623. (in Chinese) 徐静, 辛永宁, 吕维红, 等.PNPLA3 rs738409基因多态性与非酒精性脂肪性肝病遗传易感性的关系[J].中华肝脏病杂志, 2013, 21 (8) :619-623. [33]GENG N, JIANG M, ZHANG DD, et al.I148M polymorphism of PNPLA3 gene affects cell cycle of hepatoma carcinoma cell Huh-7[J].Chin J Hepatol, 2015, 23 (5) :328-332. (in Chinese) 耿宁, 姜曼, 张丁丁, 等.PNPLA3基因I148M多态性对肝癌细胞株Huh-7细胞周期的影响[J].中华肝脏病杂志, 2015, 23 (5) :328-332. [34]WANG Y, SHEN WX, LU SF, et al.Roles of microRNAs in obesity regulation[J].Chin J Diabetes, 2014, 22 (1) :89-92. (in Chinese) 王杨, 沈卫星, 卢圣锋, 等.微小RNA在肥胖中的研究进展[J].中国糖尿病杂志, 2014, 22 (1) :89-92. [35]LIN Q, GAO Z, ALARCON RM, et al.A role of miR-27 in the regulation of adipogenesis[J].Febs Journal, 2009, 276 (8) :2348. [36]ZHANG XJ.Development of microRNA-143 in obesity and insulin resistance[J].J Med Postgrad, 2013, 26 (6) :666-668. (in Chinese) 张向君.MicroRNA-143在肥胖及胰岛素抵抗中的研究进展[J].医学研究生学报, 2013, 26 (6) :666-668. [37]WANG Y, LU ZT, LI YQ, et al.miR-143 inhibits proliferation and invasion of hepatocellular carcinoma cells via down-regulation of TLR2 expression[J].Chin J cell molecular immunol, 2014, 30 (10) :1076-1079. (in Chinese) 王塬, 逯忠堂, 李尧清, 等.miR-143下调肝癌细胞TLR2的表达并抑制肝癌细胞增殖和侵袭[J].细胞与分子免疫学杂志, 2014, 30 (10) :1076-1079. [38]FU DQ, XU TW, WU WY, et al.Expression and function of microRNA-27a in hepatocellular carcinoma[J].Chin J Exp Surg, 2016, 33 (4) :1091-1093. (in Chinese) 傅德强, 许天文, 吴文艺, 等.微小RNA-27a在肝癌组织的表达及其机制[J].中华实验外科杂志, 2016, 33 (4) :1091-1093. [39]LI ZW, WU T, FU YX, et al.Expression and roles of MicroRNA-31 in HCC[J].Chin J Clin Pharmacol Ther, 2015, 20 (10) :1098-1101. (in Chinese) 李中文, 吴涛, 付应霄, 等.MicroRNA-31在肝癌中的表达和作用[J].中学临床药理学与治疗学, 2015, 20 (10) :1098-1101. [40]MAHDESSIAN H, TAXIARCHIS A, POPOV S, et al.TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content[J].Proc Natl Acad Sci U S A, 2014, 111 (24) :8913-8918. [41]JANG WY, BAE KB, KIM SH, et al.Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet[J].Biochem Biophys Res Commun, 2013, 444 (3) :296-301. [42]ZHAO HJ.Progress in the study of leptin and insulin resistance[J].Med Recapitulate, 2010, 16 (11) :1684-1687. (in Chinese) 赵荷珺.瘦素与胰岛素抵抗的研究进展[J].医学综述, 2010, 16 (11) :1684-1687.
本文二维码
计量
- 文章访问数: 1658
- HTML全文浏览量: 19
- PDF下载量: 362
- 被引次数: 0