陈博;阳惠湘;
CHEN Bo;YANG Hui-xiang;Department of Gastroenterology, Xiangya Hospital, Central South University;

• 1:中南大学湘雅医院消化内科

摘要(Abstract)：

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。
Crohn's disease(CD) is a chronic inflammatory granulomatous disease, which usually occurs at the end of the ileum and adjacent colon with segmental distribution. The pathogenesis of CD's intestinal lesions is not completely clear, which is related to multiple factors such as heredity, immunity, and environment. Adipose tissue plays an important role in the pathogenesis of CD. Recently, it has been found that visceral adipose tissue(VAT), especially its mesenteric component, i.e. creeping fat, has an impact on the disease course through its immunomodulatory properties. This paper reviews the research progress of VAT in the pathogenesis, diagnosis, and treatment of CD, in order to provide theoretical basis for clinicians.

关键词(KeyWords)： 内脏脂肪组织;爬行脂肪;克罗恩病;脂肪因子
visceral adipose tissue;creeping fat;Crohn's disease;adipokines

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81873585)~~

作者(Author): 陈博;阳惠湘;
CHEN Bo;YANG Hui-xiang;Department of Gastroenterology, Xiangya Hospital, Central South University;

Email:

DOI:

参考文献(References)：

• [1]Ramos GP,Papadakis KA.Mechanisms of Disease:Inflammatory Bowel Diseases[J].Mayo Clin Proc,2019,94:155-165．
• [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．
• [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．
• [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．
• [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．
• [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．
• [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．
• [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．
• [10]Moran GW,Dubeau MF,Kaplan GG,et al.The Increasing Weight of Crohn's Disease Subjects in Clinical Trials:AHypothesis-generatings Time-trend Analysis[J].Inflamm Bowel Dis,2013,19:2949-2956．
• [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．
• [12]Fink C,Karagiannides I,Bakirtzi K,et al.Adipose tissue and inflammatory bowel disease pathogenesis[J].Inflamm Bowel Dis,2012,18:1550-1557．
• [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．
• [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．
• [15]Schffler A,Sch9lmerich J.The role of adiponectin in inflammatory gastrointestinal diseases[J].Gut,2009,58:317-322．
• [16]Park HK,Kwak MK,Kim HJ,et al.Linking resistin,inflammation,and cardiometabolic diseases[J].Korean J Intern Med,2017,32:239-247．
• [17]Bokarewa M,Nagaev I,Dahlberg L,et al.Resistin,an adipokine with potent proinflammatory properties[J].J Immunol,2005,174:5789-5795．
• [18]Mariani F,Roncucci L.Chemerin/chemR23 axis in inflammation onset and resolution[J].Inflamm Res,2015,64:85-95．
• [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．
• [20]Drouet M,Dubuquoy L,Desreumaux P,et al.Visceral fat and gut inflammation[J].Nutrition,2012,28:113-117．
• [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．
• [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．
• [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．
• [25]Zielin'ska A,Siwin'ski P,Sobolewska-Wodarczyk A,et al.The role of adipose tissue in the pathogenesis of Crohn's disease[J].Pharmacol Rep,2019,71:105-111．
• [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．
• [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．
• [28]Bostr9m 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．
• [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．
• [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．
• [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．
• [32]Romacho T,Valencia I,Ramos-González M,et al.Visfatin/e Nampt induces endothelial dysfunction in vivo:a role for Toll-Like Receptor 4 and NLRP3 inflammasome[J].Sci Rep,2020,10:5386．
• [33]Tiaka EK,Manolakis AC,Kapsoritakis AN,et al.Unraveling 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 Protein4 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．
• [36]Borley NR,Mortensen NJ,Jewell DP,et al.The relationship 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．
• [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．
• [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．
• [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．
• [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．
• [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．
• [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．
• [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．
• [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．[44]Inflammatory Bowel Disease Group,Chinese Society of Gastroenterology,Chinese Medical Association.Chinese consensus 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．
• [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．
• [47]Osterman MT,Kundu R,Lichtenstein GR,et al.Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity:a meta-analysis[J].Gastroenterology,2006,130:1047-1053．
• [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．
• [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.