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内脏脂肪组织在克罗恩病发病、诊断及治疗中的作用

陈博 阳惠湘

陈博, 阳惠湘. 内脏脂肪组织在克罗恩病发病、诊断及治疗中的作用[J]. 协和医学杂志, 2021, 12(1): 73-79. doi: 10.3969/j.issn.1674-9081.2020.00.007
引用本文: 陈博, 阳惠湘. 内脏脂肪组织在克罗恩病发病、诊断及治疗中的作用[J]. 协和医学杂志, 2021, 12(1): 73-79. doi: 10.3969/j.issn.1674-9081.2020.00.007
CHEN Bo, YANG Hui-xiang. The Role of Visceral Adipose Tissue in the Pathogenesis, Diagnosis, and Treatment of Crohn's Disease[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(1): 73-79. doi: 10.3969/j.issn.1674-9081.2020.00.007
Citation: CHEN Bo, YANG Hui-xiang. The Role of Visceral Adipose Tissue in the Pathogenesis, Diagnosis, and Treatment of Crohn's Disease[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(1): 73-79. doi: 10.3969/j.issn.1674-9081.2020.00.007

内脏脂肪组织在克罗恩病发病、诊断及治疗中的作用

doi: 10.3969/j.issn.1674-9081.2020.00.007
基金项目: 

国家自然科学基金 81873585

详细信息
    通讯作者:

    阳惠湘  电话:0731-89753723,E-mail:yang_hx430@163.com

  • 中图分类号: R574

The Role of Visceral Adipose Tissue in the Pathogenesis, Diagnosis, and Treatment of Crohn's Disease

Funds: 

The National Natural Science Foundation of China 81873585

More Information
    Corresponding author: YANG Hui-xiang   Tel: 86-731-89753723, E-mail: yang_hx430@163.com
  • 摘要: 克罗恩病(Crohn's disease,CD)是一种慢性炎性肉芽肿性疾病,多发于末端回肠和临近结肠,呈节段性分布。CD肠道病变的机制尚不完全明确,与遗传、免疫和环境等多种因素有关。脂肪组织在CD的发病中发挥重要作用,最新研究发现内脏脂肪组织(visceral adipose tissue,VAT),特别是其肠系膜成分,亦称为爬行脂肪,可通过免疫调节特性影响CD进程。本文主要综述VAT在CD发病、诊断及治疗中的研究进展,以期为临床诊疗提供理论依据。
    作者贡献:陈博负责收集文献、撰写并修订文章; 阳惠湘负责提出选题思路,修订文章。
    利益冲突  无
  • 图  1  克罗恩病患者的病变肠切除标本[5]显示,增生的肠系膜脂肪组织(箭头)包绕肠管且超过其周长的50%,即“爬行脂肪征”

    图  2  内脏脂肪组织(紫色)的MRI定量分析影像[6]

    A.正常人; B.克罗恩病患者

    图  3  内脏脂肪组织与克罗恩病发病机制、病程及诊断的关系

    VAT:内脏脂肪组织; CRP:C反应蛋白; CD、TNF-α、IL:同表 1

    表  1  与CD相关的主要脂肪因子及功能

    脂肪因子 功能
    瘦素 促进TNF-α的产生,与TNF-α协同发挥促炎作用[13]; 调节辅助T细胞极化,通过记忆T细胞促进幼稚T细胞增殖和干扰素-γ的产生[14]
    脂联素 具有不同的亚型,表现出不同的生物学效应[15]
    抵抗素 由促炎细胞因子(IL-1、IL-6和TNF-α)诱导表达[16]; 通过NF-κB信号通路促进单核细胞表达TNF-α、IL-6和IL-12,发挥促炎活性[17]
    趋化素 通过招募和激活抗原呈递细胞在炎症早期发挥作用,连接先天免疫和获得性免疫[18]; 是促进CD炎症反应的重要因子
    CD:克罗恩病; TNF-α:肿瘤坏死因子-α; IL:白细胞介素; NF-κB:核因子-κB
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  • [1] Ramos GP, Papadakis KA. Mechanisms of Disease: Inflammatory Bowel Diseases[J]. Mayo Clin Proc, 2019, 94: 155-165. doi:  10.1016/j.mayocp.2018.09.013
    [2] Crohn BB, Ginzburg L, Oppenheimer GD. Landmark article Oct 15, 1932. Regional ileitis. A pathological and clinical entity. By Burril B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer[J]. JAMA, 1984, 251: 73-79. doi:  10.1001/jama.1984.03340250053024
    [3] Chait A, den Hartigh LJ.Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease[J]. Front Cardiovasc Med, 2020, 7: 22.
    [4] Weakley FL, Turnbull RB. Recognition of regional ileitis in the operating room[J]. Dis Colon Rectum, 1971, 14: 17-23. doi:  10.1007/BF02553169
    [5] Li Y, Zhu WM, Zuo LG, et al. The Role of the Mesentery in Crohn's Disease: The Contributions of Nerves, Vessels, Lymphatics, and Fat to the Pathogenesis and Disease Course[J]. Inflamm Bowel Dis, 2016, 22: 1483-1495. doi:  10.1097/MIB.0000000000000791
    [6] Büning C, von Kraft C, Hermsdorf M, et al. Visceral Adipose Tissue in Patients with Crohn's Disease Correlates with Disease Activity, Inflammatory Markers, and Outcome[J]. Inflamm Bowel Dis, 2015, 21: 2590-2597. doi:  10.1097/MIB.0000000000000527
    [7] Sheehan AL, Warren BF, Gear MW, et al. Fat-wrapping in Crohn's disease: pathological basis and relevance to surgical practice[J]. Br J Surg, 1992, 79: 955-958. doi:  10.1002/bjs.1800790934
    [8] Yamamoto K, Kiyohara T, Murayama Y, et al. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease[J]. Gut, 2005, 54: 789-796. doi:  10.1136/gut.2004.046516
    [9] Peyrin-Biroulet L, Chamaillard M, Gonzalez F, et al. Mesenteric fat in Crohn's disease: a pathogenetic hallmark or an innocent bystander?[J]. Gut, 2007, 56: 577-583. doi:  10.1136/gut.2005.082925
    [10] Moran GW, Dubeau MF, Kaplan GG, et al.The Increasing Weight of Crohn's Disease Subjects in Clinical Trials: A Hypothesis-generatings Time-trend Analysis[J]. Inflamm Bowel Dis, 2013, 19: 2949-2956. doi:  10.1097/MIB.0b013e31829936a4
    [11] Peyrin-Biroulet L, Gonzalez F, Dubuquoy L, et al. Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease[J]. Gut, 2012, 61: 78-85. doi:  10.1136/gutjnl-2011-300370
    [12] Fink C, Karagiannides I, Bakirtzi K, et al. Adipose tissue and inflammatory bowel disease pathogenesis[J]. Inflamm Bowel Dis, 2012, 18: 1550-1557. doi:  10.1002/ibd.22893
    [13] Raso GM, Pacilio M, Esposito E, et al. Leptin potentiates IFN-gamma-induced expression of nitric oxide synthase and cyclo-oxygenase-2 in murine macrophage J774A.1[J]. Br J Pharmacol, 2002, 137: 799-804. doi:  10.1038/sj.bjp.0704903
    [14] Arvind B, Besir O, Rainer G, et al. Leptin: a critical regulator of CD4+T-cell polarization in vitro and in vivo[J]. Endocrinology, 2010, 151: 56-62. doi:  10.1210/en.2009-0565
    [15] Schäffler A, Schölmerich J. The role of adiponectin in inflammatory gastrointestinal diseases[J]. Gut, 2009, 58: 317-322. doi:  10.1136/gut.2008.159210
    [16] Park HK, Kwak MK, Kim HJ, et al. Linking resistin, inflammation, and cardiometabolic diseases[J]. Korean J Intern Med, 2017, 32: 239-247. doi:  10.3904/kjim.2016.229
    [17] Bokarewa M, Nagaev I, Dahlberg L, et al. Resistin, an adipokine with potent proinflammatory properties[J]. J Immunol, 2005, 174: 5789-5795. doi:  10.4049/jimmunol.174.9.5789
    [18] Mariani F, Roncucci L. Chemerin/chemR23 axis in inflammation onset and resolution[J]. Inflamm Res, 2015, 64: 85-95. doi:  10.1007/s00011-014-0792-7
    [19] Carrión M, Frommer KW, Pérez-García S, et al. The Adipokine Network in Rheumatic Joint Diseases[J]. Int J Mol Sci, 2019, 20: 4091. doi:  10.3390/ijms20174091
    [20] Drouet M, Dubuquoy L, Desreumaux P, et al. Visceral fat and gut inflammation[J]. Nutrition, 2012, 28: 113-117. doi:  10.1016/j.nut.2011.09.009
    [21] Barbier M, Vidal H, Desreumaux P, et al. Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases[J]. Gastroenterol Clin Biol, 2003, 27: 987-991.
    [22] Erhayiem B, Dhingsa R, Hawkey CJ, et al. Ratio of Visceral to Subcutaneous Fat Area Is a Biomarker of Complicated Crohn's Disease[J]. Clin Gastroenterol Hepatol, 2011, 9: 684-687. doi:  10.1016/j.cgh.2011.05.005
    [23] Konstantinos K, Koutroubakis IE, Costas X, et al. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease[J]. Inflamm Bowel Dis, 2006, 12: 100-105. doi:  10.1097/01.MIB.0000200345.38837.46
    [24] Rodrigues VS, Milanski M, Fagundes JJ, et al. Serum levels and mesenteric fat tissue expression of adiponectin and leptin in patients with Crohn's disease[J]. Clin Exp Immunol, 2012, 170: 358-364. doi:  10.1111/j.1365-2249.2012.04660.x
    [25] Zielińska A, Siwiński P, Sobolewska-Włodarczyk A, et al. The role of adipose tissue in the pathogenesis of Crohn's disease[J]. Pharmacol Rep, 2019, 71: 105-111. doi:  10.1016/j.pharep.2018.09.011
    [26] Peng YJ, Shen TL, Chen YS, et al. Adiponectin and adiponectin receptor 1 overexpression enhance inflammatory bowel disease[J]. J Biomed Sci, 2018, 25: 24. doi:  10.1186/s12929-018-0419-3
    [27] Pajvani UB, Hawkins M, Combs TP, et al. Complex Distribution, Not Absolute Amount of Adiponectin, Correlates with Thiazolidinedione-mediated Improvement in Insulin Sensitivity[J]. J Biol Chem, 2004, 279: 12152-12162. doi:  10.1074/jbc.M311113200
    [28] Boström EA, Ekstedt M, Kechagias S, et al. Resistin is associated with breach of tolerance and anti-nuclear antibodies in patients with hepatobiliary inflammation[J]. Scand J Immunol, 2011, 74: 463-470. doi:  10.1111/j.1365-3083.2011.02592.x
    [29] Konrad A, Lehrke M, Schachinger V, et al. Resistin is an inflammatory marker of inflammatory bowel disease in humans[J]. Eur J Gastroenterol Hepatol, 2007, 19: 1070-1074. doi:  10.1097/MEG.0b013e3282f16251
    [30] Weigert J, Obermeier F, Neumeier M, et al. Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease[J]. Inflamm Bowel Dis, 2010, 16: 630-637. doi:  10.1002/ibd.21091
    [31] Terzoudis S, Malliaraki N, Damilakis J, et al. Chemerin, visfatin, and vaspin serum levels in relation to bone mineral density in patients with inflammatory bowel disease[J]. Eur J Gastroenterol Hepatol, 2016, 28: 814-819. doi:  10.1097/MEG.0000000000000617
    [32] Romacho T, Valencia I, Ramos-González M, et al. Visfatin/ eNampt induces endothelial dysfunction in vivo: a role for Toll-Like Receptor 4 and NLRP3 inflammasome[J]. Sci Rep, 2020, 10: 5386. doi:  10.1038/s41598-020-62190-w
    [33] Tiaka EK, Manolakis AC, Kapsoritakis AN, et al. Unravel-ing the link between leptin, ghrelin and different types of colitis[J]. Ann Gastroenterol, 2011, 24: 20-28.
    [34] Roma E, Krini M, Hantzi E, et al. Retinol Binding Protein 4 in children with Inflammatory Bowel Disease: a negative correlation with the disease activity[J]. Hippokratia, 2012, 16: 360-365.
    [35] Reinehr T, Roth CL. Inflammation Markers in Type 2 Diabetes and the Metabolic Syndrome in the Pediatric Population[J]. Curr Diab Rep, 2018, 18: 131. doi:  10.1007/s11892-018-1110-5
    [36] Borley NR, Mortensen NJ, Jewell DP, et al. The relation-ship between inflammatory and serosal connective tissue changes in ileal Crohn's disease: evidence for a possible causative link[J]. J Pathol, 2000, 190: 196-202. doi:  10.1002/(SICI)1096-9896(200002)190:2<196::AID-PATH513>3.0.CO;2-5
    [37] Li Y, Zhu WM, Gong JF, et al. Influence of exclusive enteral nutrition therapy on visceral fat in patients with Crohn's disease[J]. Inflamm Bowel Dis, 2014, 20: 1568-1574. doi:  10.1097/MIB.0000000000000114
    [38] Van Der Sloot KW, Joshi AD, Bellavance DR, et al. Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease[J]. Inflamm Bowel Dis, 2017, 23: 82-88. doi:  10.1097/MIB.0000000000000978
    [39] Uko V, Vortia E, Achkar JP, et al. Impact of abdominal visceral adipose tissue on disease outcome in pediatric Crohn's disease[J]. Inflamm Bowel Dis, 2014, 20: 2286-2291. doi:  10.1097/MIB.0000000000000200
    [40] Cravo ML, Velho S, Torres J, et al. Lower skeletal muscle attenuation and high visceral fat index are associated with complicated disease in patients with Crohn's disease: An exploratory study[J]. Clin Nutr ESPEN, 2017, 21: 79-85. doi:  10.1016/j.clnesp.2017.04.005
    [41] Holt DQ, Moore GT, Strauss BJ, et al. Visceral adiposity predicts post-operative Crohn's disease recurrence[J]. Aliment Pharmacol Ther, 2017, 45: 1255-1264. doi:  10.1111/apt.14018
    [42] Ding Z, Wu XR, Remer EM, et al. Association between high visceral fat area and postoperative complications in patients with Crohn's disease following primary surgery[J]. Colorectal Dis, 2016, 18: 163-172. doi:  10.1111/codi.13128
    [43] Maconi G, Greco S, Duca P, et al. Prevalence and clinical significance of sonographic evidence of mesenteric fat alterations in Crohn's disease[J]. Inflamm Bowel Dis, 2008, 14: 1555-1561. doi:  10.1002/ibd.20515
    [44] 中华医学会消化病学分会炎症性肠病学组.炎症性肠病诊断与治疗的共识意见(2018年, 北京)[J].中华消化杂志, 2018, 38: 292-311.

    Inflammatory Bowel Disease Group, Chinese Society of Gastroenterology, Chinese Medical Association. Chinese con-sensus on diagnosis and treatment of inflammatory bowel disease(Beijing, 2018)[J]. Zhonghua Xiao Hua Za Zhi, 2018, 38: 292-311.
    [45] Yadav DP, Madhusudhan KS, Kedia S, et al. Development and validation of visceral fat quantification as a surrogate marker for differentiation of Crohn's disease and intestinal tuberculosis[J]. J Gastroenterol Hepatol, 2017, 32: 420-426. doi:  10.1111/jgh.13535
    [46] Ko JK, Lee HL, Kim JO, et al. Visceral fat as a useful parameter in the differential diagnosis of Crohn's disease and intestinal tuberculosis[J]. Intest Res, 2014, 12: 42-47. doi:  10.5217/ir.2014.12.1.42
    [47] Osterman MT, Kundu R, Lichtenstein GR, et al. Associa-tion of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis[J]. Gastroenterology, 2006, 130: 1047-1053. doi:  10.1053/j.gastro.2006.01.046
    [48] Holt DQ, Strauss BJ, Moore GT. Weight and Body Composition Compartments do Not Predict Therapeutic Thiopurine Metabolite Levels in Inflammatory Bowel Disease[J]. Clin Transl Gastroenterol, 2016, 7: e199. doi:  10.1038/ctg.2016.56
    [49] Shen WS, Cao L, Li Y, et al. Visceral Fat Is Associated With Mucosal Healing of Infliximab Treatment in Crohn's Disease[J]. Dis Colon Rectum, 2018, 61: 706-712. doi:  10.1097/DCR.0000000000001074
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出版历程
  • 收稿日期:  2020-05-05
  • 录用日期:  2020-06-08
  • 网络出版日期:  2020-08-11
  • 刊出日期:  2021-01-30

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