Cholecalciferol (vitamin D 3) improves cognitive dysfunction and reduces inflammation in a rat fatty liver model of metabolic syndrome Oytun Erbaş a , Volkan Solmaz b, ⁎, Dürdane Aksoy b , Altuğ Yavaşoğlu c , Mustafa Sağcan d , Dilek Taşkıran e a Gaziosmanpasa University Faculty of Medicine, Department of Physiology, Tokat, Turkey b Gaziosmanpasa University Faculty of Medicine, Department of Neurology, Tokat, Turkey c Ege University School of Medicine, Department of Histology and Embryology, Izmir, Turkey d Kilis State Hospital, Department of Internal Medicine, Kilis, Turkey e Ege University School of Medicine, Department of Physiology, Izmir, Turkey abstract article info Article history: Received 27 July 2013 Accepted 29 March 2014 Available online xxxx Keywords: Fatty liver Memory functions Inflammation Cholecalciferol Aim: The aim of this study was to examine the effects of cholecalciferol on systemic inflammation and memory in the setting of fatty liver disease in rats. Materials and methods: To induce the development of fatty liver disease, the rats were fed a 35% fructose solution over 8 weeks. Group I (n = 6) was designated as the control group and fed with standard rat chow. Group II (n = 6) was provided with, standard rat chow, and 0.3 μg/kg/day of oral cholecalciferol over a duration of 2 weeks. In addition to standard rat chow, group III (n = 6) and group IV (n = 6) were given 4 mL of the 35% fructose solution per day via oral gavage for 8 weeks. However, group IV was also given 0.3 μg/kg/day of oral cholecalciferol over 2 weeks. After the treatment period, passive avoidance tasks were performed by all groups. The liver and brain were harvested for subsequent biochemical and histopathologic analyses. Key findings: The development of fatty liver extends the memory latency period of passively avoiding tasks after 1 trial. Moreover, there were increases in brain TNF-α and plasma MDA levels according to two-way analysis of variance. Cholecalciferol supplementation decreased the latency period of passively avoiding tasks in rats with hepatosteatosis, and also significantly reduced brain TNF-α and plasma MDA levels. Significance: Fatty liver may contribute to the development of systemic inflammation, which affects cognition and causes deficits in memory; however, the anti-inflammatory and antioxidant properties of vitamin D may improve the cognitive function of rats with hepatosteatosis. © 2014 Elsevier Inc. All rights reserved. Introduction Metabolic syndrome is a physiological state characterized by an increase in abdominal obesity, insulin resistance, atherogenic dyslipid- emia (a decrease in HDL with a concomitant increase in triglycerides), hypertension, and inflammation (Grundy et al., 2004). Increased adiposity and the development of fatty liver in addition to insulin resistance or type 2 diabetes mellitus are some of the most serious health outcomes in metabolic syndrome. Much research has been dedicated to understand and explain the processes contributing to metabolic syndrome. In recent years, inflammation has been found to be a causative factor of metabolic syndrome (Monteiro and Azevedo, 2010). Specifically, it has been reported that there is increased inflammation in metabolic syndrome that facilitates the development of hepatosteatosis (Sell and Eckel, 2010; Purkayastha and Cai, 2013). Cognitive dysfunction generally refers to deficits in memory and executive function, and many diseases may result in cognitive dysfunc- tion. Besides metabolic disorders, cognitive dysfunction is most often associated with advanced age such as Alzheimer's disease (Mucke, 2009). The pathogenesis of Alzheimer's disease is not yet fully understood, but a complex mechanism has been recently proposed that involves insulin resistance and an increase in inflammation. According to this theory, increased peripheral insulin resistance causes increases in serum insulin levels that trigger both peripheral and central nervous system inflammation, which induces neurotoxicity as reactive oxygen species are produced in the brain (Fishel et al., 2005). Several other studies have examined the relationship between metabolic syndrome and cognitive dysfunction (Viscogliosi et al., 2012; Roberts et al., 2010; van den Berg et al., 2007). In these studies a cause and effect relationship has not yet been fully elucidated, but inflammation has been found to be an underlying contributor to both cognitive dysfunc- tion and metabolic syndrome (Reger and Craft, 2006; Sell and Eckel, Life Sciences xxx (2014) xxx–xxx ⁎ Corresponding author. Tel.: +90 5069043459; fax: +90 3562133179. E-mail addresses: oytun.erbas@gop.edu.tr (O. Erbaş), solmaz.volkan@yahoo.com (V. Solmaz), dbekar@yahoo.com (D. Aksoy), altug.yavasoglu@ege.edu.tr (A. Yavaşoğlu), Mustafa.sagcan@mynet.com (M. Sağcan), dilek.taskiran@ege.edu.tr (D. Taşkıran). LFS-13987; No of Pages 5 http://dx.doi.org/10.1016/j.lfs.2014.03.035 0024-3205/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Please cite this article as: Erbaş O, et al, Cholecalciferol (vitamin D 3) improves cognitive dysfunction and reduces inflammation in a rat fatty liver model of metabolic synd..., Life Sci (2014), http://dx.doi.org/10.1016/j.lfs.2014.03.035