175 Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease Cem Aygun a , Omer Senturk a , Saadettin Hulagu a , Suleyman Uraz a , Altay Celebi a , Tolga Konduk a , Birsen Mutlu b and Zeynep Canturk c Objective Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. Methods Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. Results Serum adiponectin levels were 4.99 ± 2.1, 9.49 ± 3.91 and 7.74 ± 4.41 l/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P < 0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P < 0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P > 0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P = 0.013). Conclusion Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non- alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation. Eur J Gastroenterol Hepatol 18:175–180  c 2006 Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2006, 18:175–180 Keywords: adiponectin, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis a Department of Gastroenterology, b Department of Microbiology and c Department of Endocrinology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey Correspondence and requests for reprints to Cem Aygun, Fahrettin Kerim Gokay Cad No. 282/10, 34781 Erenkoy, Istanbul, Turkey Tel: +90 532 713 04 91; fax: +90 262 233 54 88; e-mail: caygun1@yahoo.com Received 17 May 2005 Accepted 3 October 2005 Introduction Adiponectin, also known as adipocyte complement- related protein of 30 kDa (ACRP30), is a recently isolated protein that is a product of the adipose tissue-specific transcript-1 (apM1) gene [1]. It is mostly expressed in white adipose tissue having a 244-amino acid base structure, with a high sequence homology to collagen VII, collagen X and complement C1q and a high struc- tural similarity to tumour necrosis factor-a (TNF-a) [2– 4]. Adiponectin is induced during adipocyte differentia- tion, and its secretion is stimulated by insulin and binds to two different receptors termed AdipoR1 and AdipoR2 [5]. AdipoR1 is found primarily in skeletal muscle whereas AdipoR2 is primarily found in hepatic tissue [6]. The physiological role of adiponectin is not yet fully determined, but experimental findings had shown that it has an inhibitory effect on proliferation of myelomono- cytic progenitors as well as on phagocytic activity and TNF-a production by macrophages, which are findings consistent with an anti-inflammatory effect of this protein [7]. In chronic liver injury, in contrast to harmful effects of proinflammatory cytokines, anti-inflammatory cytokines have been shown to have a hepatoprotective role, so it has been postulated that there is an imbalance between proinflammatory and anti-inflammatory cytokines in the mechanisim. As a recently found anti-inflammatory protein, the three-dimensional structure of adiponectin molecule closely resembles that of TNF-a, while inter- estingly these two proteins are found to have completely opposite effects [4]. Both in-vivo and in-vitro experi- ments demonstrated that adiponectin and TNF-a sup- press production of each other and also antagonize each 0954-691X  c 2006 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.