ORIGINAL ARTICLE Hypertrophic Mesenteric Adipose Tissue May Play a Role in Atherogenesis in Inﬂammatory Bowel Diseases Eleni Theocharidou, MD, MSc,* Aikaterini Balaska, BSc,* Konstantinos Vogiatzis, BSc,* Constantinos C. Tellis, PhD, † Thomas D. Gossios, MD, ‡ Vasilios G. Athyros, MD, PhD,* Alexandros D. Tselepis, MD, PhD, † and Asterios Karagiannis, MD, PhD* Background: Adipokines released by the adipose tissue are known to play a role in atherogenesis. The hypertrophic mesenteric fat in patients with inﬂammatory bowel diseases (IBD) also produces adipokines that are considered to play a role in intestinal inﬂammation. Whether they also contribute to accelerated atherosclerosis in IBD is unknown. The aim of this study was to assess the role of 2 adipokines, resistin and adiponectin, in IBD. Methods: We previously published data on 3 markers of cardiovascular risk, carotid intima-media thickness, carotid-femoral pulse wave velocity, and lipoprotein-associated phospholipase A2, in 44 patients with IBD and 44 controls matched for established cardiovascular risk factors. In this study, we measured resistin and adiponectin levels, and assessed their correlations with carotid intima-media thickness, pulse wave velocity, and lipoprotein- associated phospholipase A2. Results: Resistin levels were signiﬁcantly higher in patients with IBD (13.7 versus 10 ng/mL; P ¼ 0.022), but there was no difference in adiponectin levels. Resistin levels were signiﬁcantly higher in patients with active disease compared with those in remission (18.9 versus 11.3 ng/mL; P ¼ 0.014). Adiponectin levels were signiﬁcantly lower in Crohn’s disease compared with ulcerative colitis (6736.3 6 3105 versus 10,476.1 6 5575.7 ng/mL; P ¼ 0.026). Adiponectin correlated inversely with pulse wave velocity (rho ¼ 20.434; P , 0.0005) and carotid intima-media thickness (rho ¼ 20.255; P ¼ 0.021). Conclusions: This is the ﬁrst study to suggest that adipokines produced by the hypertrophic mesenteric fat in IBD may play a role not only in intestinal inﬂammation but also in atherogenesis. Resistin has mainly pro-inﬂammatory properties, whereas adiponectin likely exerts an angioprotective effect. (Inﬂamm Bowel Dis 2016;22:2206–2212) Key Words: inﬂammatory bowel diseases, arterial stiffness, lipoprotein-associated phospholipase A2, adipokines, resistin, adiponectin T he perception on the role of adipose tissue has shifted from plain storage of fat to more complex endocrine and paracrine functions. The adipose tissue has the ability to synthesize and release a variety of molecules into the systemic circulation, includ- ing pro-inﬂammatory cytokines and adipokines. These molecules play a regulatory role in insulin resistance, lipid and glucose metabolism, and have an effect on endothelial function. The dis- covery of these properties elucidated the potential role of adipo- kines in atherogenesis. “Creeping fat,” the hypertrophic adipose tissue that extends from the mesentery and partially covers (.50% of the perimeter) the surface of the inﬂamed intestine, is a feature unique to inﬂam- matory bowel diseases (IBD). This hypertrophic mesenteric fat produces pro- and anti-inﬂammatory molecules likely in response to bacterial translocation from the gut, 1 including adipokines (mainly leptin, adiponectin, and resistin) and pro-inﬂammatory cytokines nonspeciﬁc to adipose tissue, such as tumor necrosis factor a (TNF-a), interleukins 6 and 8. Leptin, a pro-inﬂammatory cytokine, suppresses the appetite and is produced in amounts pro- portionate to whole body fat. 2 Adiponectin has anti-inﬂammatory properties and seems to play a protective role against the devel- opment of the metabolic syndrome. 3 Its synthesis correlates inversely with whole body fat. Resistin increases with obesity, and seems to play a pro-inﬂammatory role. 4 The role of the mesenteric adipose tissue and adipokines in the pathogenesis of IBD has been an area of increasing interest. Increased leptin levels have been found in the enteric lumen of patients with IBD, 5 and experimental studies demonstrated that leptin induces intestinal inﬂammation in IBD. 6 Adiponectin release from the mesenteric adipose tissue is increased in IBD in contrast to reduced synthesis in obesity. 7 A study in 100 pa- tients with IBD showed increased adiponectin and resistin, and reduced leptin levels in the systemic circulation of patients with IBD compared with 60 healthy controls. 8 Adipokine levels did not correlate with disease activity, but anti–TNF-a therapy resulted in Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.ibdjournal.org). Received for publication February 21, 2016; Accepted May 12, 2016. From the *2nd Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; † Lab- oratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece; and ‡ 1st Department of Cardiology, AHEPA General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. The authors have no conﬂict of interest to disclose. Address correspondence to Eleni Theocharidou, MD, MSc, 1 K. Alexandridi Street, 62125, Serres, Greece (e-mail: eltheocharidou@hotmail.com). Copyright © 2016 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000873 Published online 9 August 2016. 2206 | www.ibdjournal.org Inﬂamm Bowel Dis  Volume 22, Number 9, September 2016 Copyright © 2016 Crohn’s & Colitis Foundation of America, Inc. Unauthorized reproduction of this article is prohibited.