Serum pigment epithelium-derived factor levels are increased in patients with biopsy-proven nonalcoholic fatty liver disease and independently associated with liver steatosis Yusuf Yilmaz a, b, ⁎ , 1 , Fatih Eren b, 1 , Talat Ayyildiz c , Yasar Colak d , Ramazan Kurt a, b , Ebubekir Senates e , Ilyas Tuncer d , Enver Dolar c , Nese Imeryuz a, b a Department of Gastroenterology, Marmara University, School of Medicine, Pendik, 34899 Istanbul, Turkey b Institute of Gastroenterology, Marmara University, Maltepe, Istanbul, Turkey c Department of Gastroenterology, Uludag University Medical School, Bursa, Turkey d Department of Gastroenterology, Goztepe Education and Research Hospital, Istanbul, Turkey e Department of Gastroenterology, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey abstract article info Article history: Received 28 July 2011 Received in revised form 8 August 2011 Accepted 18 August 2011 Available online 24 August 2011 Keywords: Pigment epithelium-derived factor Nonalcoholic fatty liver disease Enzyme-linked immunosorbent assay Steatosis Background: Increased serum concentrations of pigment epithelium-derived factor (PEDF) have been linked to the metabolic syndrome in the general population. However, the relationship between serum PEDF and nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, remains un- known. Methods: We assayed serum PEDF levels in 156 patients with biopsy-proven NAFLD and 103 nonsteatotic control subjects who were matched for age and sex. The association between levels of PEDF and clinical, bio- chemical, and histological phenotypes was examined. Results: NAFLD patients had significantly higher serum PEDF levels (1.97 ± 0.50 μg/mL) than control subjects (1.51 ± 0.49 μg/mL, Student's t test, P b 0.001). Multivariable-adjusted stepwise regression analysis showed that PEDF ([beta] = 0.32, t = 3.13, P = 0.002) and triglycerides ([beta] = 0.22, t = 2.23, P = 0.02) were, in the order they entered into the model, the main independent predictors of steatosis scores in our patients with NAFLD. Conclusions: Serum PEDF levels are significantly increased in patients with biopsy-proven NAFLD and are as- sociated with liver steatosis independently of traditional risk factors. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Nonalcoholic fatty liver disease (NAFLD), which includes a disease spectrum ranging from simple steatosis to nonalcoholic steatohepati- tis (NASH) and cirrhosis, is the most common liver disease identified in Western countries [1,2]. NAFLD has also become a significant form of chronic liver disease in developing counties [3]. NAFLD is strongly associated with a number of metabolic comorbidities, such as obesity, diabetes, hypertension, and atherogenic dyslipidemia, and it is now recognised as the hepatic manifestation of the metabolic syndrome (MS) [4], with insulin resistance universally considered as the main pathogenetic mechanism [5]. Pigment epithelium-derived factor (PEDF) is a secreted glycopro- tein produced from a variety of tissues which acts as an anti- angiogenic, anti-inflammatory, and anti-oxidant molecule [6–11]. In addition, it is an adipocyte-secreted factor involved in the develop- ment of insulin resistance [12]. Borg et al. [13] have reported that PEDF has a role in lipid metabolism by promoting lipolysis. Impor- tantly, increasing evidence indicates that PEDF may play a role in the pathogenesis of visceral adiposity, the metabolic syndrome, and diabetes. Sabater et al. [14] have reported that circulating PEDF levels are positively associated with body mass index, waist-to-hip ratio, glycated haemoglobin, and fasting triglycerides and negatively with insulin sensitivity. Chen et al. [15] demonstrated that plasma PEDF is significantly associated with the presence of the metabolic syn- drome and predicted the development of the metabolic syndrome in Chinese men. Tschoner et al. [16] have also reported that weight loss is associated with a reduction of serum pigment epithelium- derived factor levels in severely obese adults undergoing bariatric surgery. Although metabolic alterations and insulin resistance are main contributors to the prevalence of NAFLD [1–3], there is a paucity of data regarding the potential association between serum PEDF levels and biopsy-proven NAFLD in adult patients. In this study, we Clinica Chimica Acta 412 (2011) 2296–2299 ⁎ Corresponding author at: Department of Gastroenterology, Marmara University, School of Medicine, Pendik, 34899 Istanbul, Turkey. Tel.: +90 5334403995; fax: +90 2166886681. E-mail address: yusufyilmaz@uludag.edu.tr (Y. Yilmaz). 1 These authors contributed equally to this work. 0009-8981/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2011.08.025 Contents lists available at SciVerse ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim