Leading article 1035 Resistin: another rising biomarker in inflammatory bowel disease? Konstantinos Karmiris and Ioannis E. Koutroubakis K Resistin is a 12.5-kDa cysteine-rich adipokine produced in white adipose tissue (WAT) and exerting pro-inflammatory properties. K It is overproduced in vitro from immune cells and adipocytes as well as in vivo in various acute and chronic inflammatory diseases. K In IBD patients, resistin has been measured and found increased in serum and mesenteric WAT. K Resistin could be suggested as a valuable marker of disease activity but certain issues need first clarification before adopting this notion. The researchers’ view regarding the role of white adipose tissue (WAT) in inflammation has been greatly transformed over the last 10 years. WAT is now considered as an active organ producing many crucial molecules called adipokines. Resistin is a recently discovered cysteine-rich adipokine that has emerged during this decade as a promising inflammatory marker in various diseases. It is synthesized either from adipocytes or from immune cells, and exerts a pro-inflammatory profile in a variety of different experimental settings. Inflammatory bowel disease (IBD) is characterized by anorexia, malnutrition, altered body composition and the development of mesenteric WAT hypertrophy. The study by Konrad-Zerna et al. in this issue of the journal demonstrates an increased serum resistin in IBD patients, this being in agreement with previous IBD studies in mesenteric WAT and serum. Interesting aspects like the true validity of resistin as a marker of disease activity, the role of its different molecular isoforms, the cells that predominantly produce this molecule, and the possible use of resistin as a guide for therapeutic interventions, arise. Eur J Gastroenterol Hepatol 19:1035–1037  c 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2007, 19:1035–1037 Keywords: adipokines, Crohn’s disease, resistin, ulcerative colitis Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece Correspondence to Ioannis E. Koutroubakis, MD, PhD, Assistant Professor of Medicine, Department of Gastroenterology, University Hospital Heraklion, PO Box 1352, 71110 Heraklion, Crete, Greece Tel: + 302810392253; fax: + 302810542085; e-mail: ktjohn@her.forthnet.gr Received 2 August 2007 Accepted 14 August 2007 Intensive research since the mid-1990s has shown white adipose tissue (WAT) as an important endocrine and signaling tissue. Different subpopulations of WAT cells (adipocytes, matrix cells, stromovascular cells, macro- phages and mast cells) produce and release various bioactive proteins and multifunctional molecules that interact with the microenvironment, not only in an autocrine/paracrine, but also an endocrine mode of action. These products are collectively called ‘adipokines’ [1]. Inflammation and immunity have been closely correlated with WAT, based on the fact that many adipokines are inflammation-related proteins. Following the observation that obesity is a state of low-grade inflammation, adipokines were correlated with various chronic inflam- matory diseases [2]. Anorexia, malnutrition, altered body composition and development of mesenteric WAT hypertrophy (accumulation of intra-abdominal mWAT) are well known features of inflammatory bowel diseases (IBDs), especially Crohn’s disease (CD). An aberrance in adipokines’ secretion seems to be critically involved into the pathogenesis of IBD [3]. Resistin is a 12.5-kDa cysteine-rich peptide consisting of 108 amino acids. It is composed of a signal peptide, a variable region, and a conserved C-terminus [4]. It belongs to a family of resistin-like molecules with distinct expression patterns and biological effects [5]. It circu- lates in humans in a concentration between 7 and 22 ng/ml. The mature protein has a tendency to form oligomers, thus circulating in human serum in several different lower molecular weight and higher molecular weight isoforms [6]. Resistin is mainly expressed in humans in peripheral blood mononuclear cells (PBMC), macrophages and bone marrow cells [7,8]. Expression and production from human adipocytes is either favored [9,10] or confuted in the literature [11]. During fasting, resistin parallels glucose and insulin, thus it is decreased, while it is restored upon re-feeding. It is upregulated in response to growth hormone, hyper- glycemia, dexamethasone and endothelin-1, and is downregulated in response to insulin, thiazolidinediones, somatropin, epinephrine, isoproterenol and PPARg 0954-691X  c 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.