ORIGINAL ARTICLE Circulating Levels of Leptin, Adiponectin, Resistin, and Ghrelin in Inﬂammatory Bowel Disease Konstantinos Karmiris, MD, Ioannis E. Koutroubakis, MD, Costas Xidakis, Maria Polychronaki, MD, Theodora Voudouri, and Elias A. Kouroumalis, MD, PhD Background: There is evidence that adipocytokines play an impor- tant role in metabolism and in inﬂammation. Because human metab- olism dramatically changes in inﬂammatory bowel disease (IBD) and chronic inﬂammation is the hallmark of the disease, we studied serum levels of leptin, adiponectin, resistin, and ghrelin in patients with ulcerative colitis (UC) and Crohn’s disease (CD) in comparison with healthy controls (HC). Methods: Leptin, adiponectin, resistin, and active ghrelin serum levels were measured in 100 IBD patients (46 UC and 54 CD) and in 60 matched HC using commercially available enzyme-linked immu- nosorbent assays. Leptin, adiponectin, resistin, and ghrelin levels were correlated with disease activity, type, localization, and treatment. Results: Mean serum leptin levels were 10.6 6 2.0 ng/mL in UC patients, 12.5 6 2.6 ng/mL in CD patients, and 15.0 6 1.8 ng/mL in HC (P = .01). Mean serum adiponectin levels were 9514.8 6 787.8 ng/mL in UC patients, 7651.1 6 613 ng/mL in CD patients, and 7270.6 6 559.4 ng/mL in HC (P = .05). Mean serum resistin levels were 21.2 6 2.2 ng/mL in UC patients, 18.7 6 1.6 ng/mL in CD patients and 11.8 6 0.6 ng/mL in HC (P = .0002). Mean serum ghrelin levels were 48.2 6 4.2 pg/mL in UC patients, 49.4 6 4.6 pg/mL in CD patients and 14.8 6 3.0 pg/mL in HC (P , .0001). Serum levels of these adipocytokines were not correlated with either C-reactive protein levels or the clinical indices of activity. No asso- ciation between serum adipocytokines levels and disease localization in both UC and CD patients was found. Only serum ghrelin was signiﬁcantly higher in ileal compared with colonic CD (P = .04). Conclusions: Serum levels of adiponectin, resistin, and active ghrelin are increased whereas serum levels of leptin are decreased in patients with IBD. Further studies are needed to elucidate the role of adipocytokines in IBD. Key Words: adiponectin, Crohn’s disease, ghrelin, leptin, resistin, ulcerative colitis (Inﬂamm Bowel Dis 2006;12:100–105) R ecent studies suggest that white adipose tissue (WAT), besides its ability to respond to afferent signals from tra- ditional hormone systems and the central nervous system, also expresses and secretes factors with important functions, col- lectively called adipocytokines. 1 There is evidence that adipocytokines are involved in inﬂammatory and metabolic pathways in humans. Among the adipocytokines, leptin, adiponectin, and resistin appear to play an important role. 2 Anorexia, malnutrition, altered body composition, and development of mesenteric obesity (accumulation of intra- abdominal WAT), are well-known features of inﬂammatory bowel disease (IBD), mainly of Crohn’s disease (CD), indi- cating an important role for WAT-secreted proteins. 3 Over- expression of adipocytokines such as leptin, adiponectin, and resistin in mesenteric adipose tissue of patients with CD who have been operated on has recently been reported, suggesting that mesenteric adipocytes in IBD may act as immunoregu- latory cells. 4–6 Therefore, it is suggested that adipocytokines may participate in the disease pathogenesis. 7 Leptin is a 16-kDa nonglycosylated protein, which belongs to the type I cytokine superfamily and is characterized by a long-chain 4-helical bundle structure. 8 Leptin possesses proinﬂammatory as well as anti-inﬂammatory properties ac- cording to the experimental conditions. 9 Its role in IBD has been studied, but the results are conﬂicting, therefore further investigation is required. 10–13 Adiponectin is an approximately 30-kDa polypeptide, 14 and interestingly, the terminal structure of its globular domain bears a striking similarity to tumor necrosis factor-a (TNF-a), despite a lack of homology in primary sequence. 15 Adipo- nectin appears to have anti-inﬂammatory properties because of its antagonism against TNF-a. Various experiments have demonstrated that adiponectin and TNF-a suppress each other’s production and also antagonize each other’s action in their target tissues. 16–19 Overexpression of adiponectin in the Received for publication September 1, 2005; accepted December 1, 2005. From the Department of Gastroenterology, University Hospital, Heraklion, Crete, Greece. Reprints: Ioannis E. Koutroubakis, MD, Department of Gastroenterology, University Hospital Heraklion, PO Box 1352, 71110 Heraklion, Crete, Greece (e-mail: ktjohn@her.forthnet.gr) Copyright Ó 2006 by Lippincott Williams & Wilkins 100 Inﬂamm Bowel Dis  Volume 12, Number 2, February 2006 Copyright ' Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.