Wnt1 inducible protein-1 signaling pathway (WISP-1) is a relatively new adipokine involved in many cellular processes, including epithelial mucosa healing. The aim of the study was to compare circulating levels of WISP-1 and other selected adipokines [adiponectin, resistin and retinol-binding protein 4 (RBP-4)] in children with inflammatory bowel disease (IBD) with healthy controls and to investigate possible differences between Crohn's disease patients. (CD) or ulcerative colitis (UC). The study was performed as a case-control study. In addition to adipokines, anthropometric, lipid parameters, markers of inflammation or disease activity were evaluated in all participants. Compared to healthy controls (n=20), significantly lower levels of adiponectin and higher levels of resistin and WISP-1 were found in patients with IBD (n=58). Elevation of WISP-1 was detected only in the CD group (n=31). There were no differences in RBP-4 levels between the groups. Adiponectin, WISP-1 and RBP-4 were independently associated with body mass index only, resistin levels were associated with C-reactive protein levels and leukocyte counts. Adverse adipokines production reflects presence of dysfunctional fat tissue in IBD patients. Higher levels of WISP-1 in CD compared to patients with UC may indicate a specific role for mesenteric adipose tissue in WISP-1 production.

3rd Department of Internal Medicine Nephrology Rheumatology and Endocrinology Faculty of Medicine and Dentistry University Hospital and Palacky University Olomouc Czech Republic

See more in PubMed

Bousvaros A. Use of immunomodulators and biologic therapies in children with inflammatory bowel disease. Expert Rev Clin Immunol. 2010;6:659–666. doi: 10.1586/eci.10.46. PubMed DOI

Gonçalves P, Magro F, Martel F. Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel. Inflamm Bowel Dis. 2015;21:453–467. doi: 10.1097/MIB.0000000000000209. PubMed DOI

Schwarz J, Vecka M, Stožický F, Pomahačová R, Staňková B, Tvrzická E, Kreslová M, Zahálková R, Sýkora J. The assessment of plasma fatty acid profiles in newly diagnosed treatment-naive paediatric Crohn’s disease. Physiol Res. 2021;70:799–808. doi: 10.33549/physiolres.934665. PubMed DOI PMC

Lackeyram D, Young D, Kim CJ, Yang C, Archbold TL, Mine Y, Fan MZ. Interleukin-10 is differentially expressed in the small intestine and the colon experiencing chronic inflammation and ulcerative colitis induced by dextran sodium sulfate in young pigs. Physiol Res. 2017;66:147–162. doi: 10.33549/physiolres.933259. PubMed DOI

Karaskova E, Velganova-Veghova M, Geryk M, Foltenova H, Kucerova V, Karasek D. Role of Adipose Tissue in Inflammatory Bowel Disease. Int J Mol Sci. 2021;22:4226. doi: 10.3390/ijms22084226. PubMed DOI PMC

Weidinger C, Ziegler JF, Letizia M, Schmidt F, Siegmund B. Adipokines and Their Role in Intestinal Inflammation. Front Immunol. 2018;9:1974. doi: 10.3389/fimmu.2018.01974. PubMed DOI PMC

Wang HH, Luo WY, Lin M, Li XJ, Xiang GD, Triganti DS. Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease. Physiol Res. 2021;70:203–211. doi: 10.33549/physiolres.934547. PubMed DOI PMC

Morshedzadeh N, Rahimlou M, Asadzadeh Aghdaei H, Shahrokh S, Reza Zali M, Mirmiran P. Association Between Adipokines Levels with Inflammatory Bowel Disease (IBD): Systematic Reviews. Dig Dis Sci. 2017;62:3280–3286. doi: 10.1007/s10620-017-4806-5. PubMed DOI

Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun. 2004;316:924–929. doi: 10.1016/j.bbrc.2004.02.130. PubMed DOI

Singh UP, Singh NP, Guan H, Busbee B, Price RL, Taub DD, Mishra MK, Fayad R, Nagarkatti M, Nagarkatti PS. The emerging role of leptin antagonist as potential therapeutic option for inflammatory bowel disease. Int Rev Immunol. 2014;33:23–33. doi: 10.3109/08830185.2013.809071. PubMed DOI PMC

Sitaraman S, Liu X, Charrier L, Gu LH, Ziegler TR, Gewirtz A, Merlin D. Colonic leptin: source of a novel proinflammatory cytokine involved in IBD. FASEB J. 2004;18:696–698. doi: 10.1096/fj.03-0422fje. PubMed DOI

Harper JW, Zisman TL. Interaction of obesity and inflammatory bowel disease. World J Gastroenterol. 2016;22:7868–7881. doi: 10.3748/wjg.v22.i35.7868. PubMed DOI PMC

Eder P, Adler M, Dobrowolska A, Kamhieh-Milz J, Witowski J. The Role of Adipose Tissue in the Pathogenesis and Therapeutic Outcomes of Inflammatory Bowel Disease. Cells. 2019;8:628. doi: 10.3390/cells8060628. PubMed DOI PMC

Karmiris K, Koutroubakis IE, Xidakis C, Polychronaki M, Kouroumalis EA. The effect of infliximab on circulating levels of leptin, adiponectin and resistin in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2007;19:789–794. doi: 10.1097/MEG.0b013e3282202bca. PubMed DOI

Valentini L, Wirth EK, Schweizer U, Hengstermann S, Schaper L, Koernicke T, Dietz E, Norman K, Buning C, Winklhofer-Roob BM, Lochs H, Ockenga J. Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease. Nutrition. 2009;25:172–181. doi: 10.1016/j.nut.2008.07.020. PubMed DOI

Roma E, Krini M, Hantzi E, Sakka S, Panayiotou I, Margeli A, Papassotiriou I, Kanaka-Gantenbein C. Retinol Binding Protein 4 in children with Inflammatory Bowel Disease: a negative correlation with the disease activity. Hippokratia. 2012;16:360–365. PubMed PMC

Perbal B, Tweedie S, Bruford E. The official unified nomenclature adopted by the HGNC calls for the use of the acronyms, CCN1–6, and discontinuation in the use of CYR61, CTGF, NOV and WISP 1–3 respectively. J Cell Commun Signal. 2018;12:625–629. doi: 10.1007/s12079-018-0491-1. PubMed DOI PMC

Feng M, Jia S. Dual effect of WISP-1 in diverse pathological processes. Chin J Cancer Res. 2016;28:553–560. doi: 10.21147/j.issn.1000-9604.2016.06.01. PubMed DOI PMC

Barchetta I, Cimini FA, Capoccia D, De Gioannis R, Porzia A, Mainiero F, Di Martino M, Bertoccini L, De Bernardinis M, Leonetti F, Baroni MG, Lenzi A, Cavallo MG. WISP1 Is a Marker of Systemic and Adipose Tissue Inflammation in Dysmetabolic Subjects With or Without Type 2 Diabetes. J Endocr Soc. 2017;1:660–670. doi: 10.1210/js.2017-00108. PubMed DOI PMC

Murahovschi V, Pivovarova O, Ilkavets I, Dmitrieva RM, Döcke S, Keyhani-Nejad F, Gögebakan Ö, Osterhoff M, Kemper M, Hornemann S, Markova M, Klöting N, Stockmann M, Weickert MO, Lamounier-Zepter V, Neuhaus P, Konradi A, Dooley S, von Loeffelholz C, Blüher M, Pfeiffer AF, Rudovich N. WISP1 is a novel adipokine linked to inflammation in obesity. Diabetes. 2015;64:856–866. doi: 10.2337/db14-0444. PubMed DOI

Levine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L, Kolho KL, Veres G, Russell RK, Paerregaard A, Buderus S, Greer ML, Dias JA, Veereman-Wauters G, Lionetti P, Sladek M, Martin de Carpi J, Staiano A, Ruemmele FM, Wilson DC European Society of Pediatric Gastroenterology, Hepatology and Nutrition. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr. 2014;58:795–806. doi: 10.1097/MPG.0000000000000239. PubMed DOI

Hyams J, Markowitz J, Otley A, Rosh J, Mack D, Bousvaros A, Kugathasan S, Pfefferkorn M, Tolia V, Evans J, Treem W, Wyllie R, Rothbaum R, del Rosario J, Katz A, Mezoff A, Oliva-Hemker M, Lerer T, Griffiths A Pediatric Inflammatory Bowel Disease Collaborative Research Group. Evaluation of the pediatric crohn disease activity index: a prospective multicenter experience. J Pediatr Gastroenterol Nutr. 2005;41:416–421. doi: 10.1097/01.mpg.0000183350.46795.42. PubMed DOI

Turner D, Hyams J, Markowitz J, Lerer T, Mack DR, Evans J, Pfefferkorn M, Rosh J, Kay M, Crandall W, Keljo D, Otley AR, Kugathasan S, Carvalho R, Oliva-Hemker M, Langton C, Mamula P, Bousvaros A, LeLeiko N, Griffiths AM Pediatric IBD Collaborative Research Group. Appraisal of the pediatric ulcerative colitis activity index (PUCAI) Inflamm Bowel Dis. 2009;15:1218–1223. doi: 10.1002/ibd.20867. PubMed DOI

Zhang Q, Zhang C, Li X, Yu Y, Liang K, Shan X, Zhao K, Niu Q, Tian Z. WISP1 Is increased in intestinal mucosa and contributes to inflammatory cascades in inflammatory bowel disease. Dis Markers. 2016;2016:3547096. doi: 10.1155/2016/3547096. PubMed DOI PMC

Moparthi L, Koch S. Wnt signaling in intestinal inflammation. Differentiation. 2019;108:24–32. doi: 10.1016/j.diff.2019.01.002. PubMed DOI

Quiros M, Nishio H, Neumann PA, Siuda D, Brazil JC, Azcutia V, Hilgarth R, O’Leary MN, Garcia-Hernandez V, Leoni G, Feng M, Bernal G, Williams H, Dedhia PH, Gerner-Smidt C, Spence J, Parkos CA, Denning TL, Nusrat A. Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling. J Clin Invest. 2017;127:3510–3520. doi: 10.1172/JCI90229. PubMed DOI PMC

Tacke C, Aleksandrova K, Rehfeldt M, Murahovschi V, Markova M, Kemper M, Hornemann S, Kaiser U, Honig C, Gerbracht C, Kabisch S, Hörbelt T, Ouwens DM, Weickert MO, Boeing H, Pfeiffer AFH, Pivovarova O, Rudovich N. Assessment of circulating Wnt1 inducible signalling pathway protein 1 (WISP-1)/CCN4 as a novel biomarker of obesity. J Cell Commun Signal. 2018;12:539–548. doi: 10.1007/s12079-017-0427-1. PubMed DOI PMC

Uko V, Vortia E, Achkar JP, Karakas P, Fiocchi C, Worley S, Kay MH. Impact of abdominal visceral adipose tissue on disease outcome in pediatric Crohn's disease. Inflamm Bowel Dis. 2014;20:2286–2291. doi: 10.1097/MIB.0000000000000200. PubMed DOI

Rodrigues VS, Milanski M, Fagundes JJ, Torsoni AS, Ayrizono ML, Nunez CE, Dias CB, Meirelles LR, Dalal S, Coy CS, Velloso LA, Leal RF. Serum levels and mesenteric fat tissue expression of adiponectin and leptin in patients with Crohn's disease. Clin Exp Immunol. 2012;170:358–364. doi: 10.1111/j.1365-2249.2012.04660.x. PubMed DOI PMC

Kahraman R, Calhan T, Sahin A, Ozdil K, Caliskan Z, Bireller ES, Cakmakoglu B. Are adipocytokines inflammatory or metabolic mediators in patients with inflammatory bowel disease? Ther Clin Risk Manag. 2017;13:1295–1301. doi: 10.2147/TCRM.S140618. PubMed DOI PMC

Karmiris K, Koutroubakis IE, Xidakis C, Polychronaki M, Voudouri T, Kouroumalis EA. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12:100–105. doi: 10.1097/01.MIB.0000200345.38837.46. PubMed DOI

Weigert J, Obermeier F, Neumeier M, Wanninger J, Filarsky M, Bauer S, Aslanidis C, Rogler G, Ott C, Schäffler A, Schölmerich J, Buechler C. Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease. Inflamm Bowel Dis. 2010;16:630–637. doi: 10.1002/ibd.21091. PubMed DOI

Waluga M, Hartleb M, Boryczka G, Kukla M, Zwirska-Korczala K. Serum adipokines in inflammatory bowel disease. World J Gastroenterol. 2014;20:6912–6917. doi: 10.3748/wjg.v20.i22.6912. PubMed DOI PMC

Chouliaras G, Panayotou I, Margoni D, Mantzou E, Pervanidou P, Manios Y, Chrousos GP, Roma E. Circulating leptin and adiponectin and their relation to glucose metabolism in children with Crohn's disease and ulcerative colitis. Pediatr Res. 2013;74:420–426. doi: 10.1038/pr.2013.114. PubMed DOI

Ortega Moreno L, Sanz-Garcia A, Fernández de la Fuente MJ, Arroyo Solera R, Fernández-Tomé S, Marin AC, Mora-Gutierrez I, Fernández P, Baldan-Martin M, Chaparro M, Gisbert JP, Bernardo D. Serum adipokines as non-invasive biomarkers in Crohn's disease. Sci Rep. 2020;10:18027. doi: 10.1038/s41598-020-74999-6. PubMed DOI PMC

Murray KA, Hoad CL, Garratt J, Kaviani M, Marciani L, Smith JK, Siegmund B, Gowland PA, Humes DJ, Spiller RC. A pilot study of visceral fat and its association with adipokines, stool calprotectin and symptoms in patients with diverticulosis. PLoS One. 2019;14:e0216528. doi: 10.1371/journal.pone.0216528. PubMed DOI PMC

Konrad A, Lehrke M, Schachinger V, Seibold F, Stark R, Ochsenkühn T, Parhofer KG, Göke B, Broedl UC. Resistin is an inflammatory marker of inflammatory bowel disease in humans. Eur J Gastroenterol Hepatol. 2007;19:1070–1074. doi: 10.1097/MEG.0b013e3282f16251. PubMed DOI

Chen CC, Li TC, Li CI, Liu CS, Wang HJ, Lin CC. Serum resistin level among healthy subjects: relationship to anthropometric and metabolic parameters. Metabolism. 2005;54:471–475. doi: 10.1016/j.metabol.2004.10.015. PubMed DOI

Norata GD, Ongari M, Garlaschelli K, Raselli S, Grigore L, Catapano AL. Plasma resistin levels correlate with determinants of the metabolic syndrome. Eur J Endocrinol. 2007;156:279–284. doi: 10.1530/eje.1.02338. PubMed DOI

Stejskal D, Adamovská S, Bartek J, Juráková R, Prosková J. Resistin - concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2003;147:63–69. doi: 10.5507/bp.2003.009. PubMed DOI

Jové M, Planavila A, Cabrero A, Novell F, Ros E, Zambón D, Laguna JC, Carrera MV. Reductions in plasma cholesterol levels after fenofibrate treatment are negatively correlated with resistin expression in human adipose tissue. Metabolism. 2003;52:351–355. doi: 10.1053/meta.2003.50055. PubMed DOI

Wessel H, Saeed A, Heegsma J, Connelly MA, Faber KN, Dullaart RPF. Plasma Levels of Retinol Binding Protein 4 Relate to Large VLDL and Small LDL Particles in Subjects with and without Type 2 Diabetes. J Clin Med. 2019;8:1792. doi: 10.3390/jcm8111792. PubMed DOI PMC

Vergès B, Guiu B, Cercueil JP, Duvillard L, Robin I, Buffier P, Bouillet B, Aho S, Brindisi MC, Petit JM. Retinol-binding protein 4 is an independent factor associated with triglycerides and a determinant of very low-density lipoprotein-apolipoprotein B100 catabolism in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2012;32:3050–3057. doi: 10.1161/ATVBAHA.112.255190. PubMed DOI

Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease