Background and aim. Non-alcoholic fatty liver disease (NAFLD) is a very common chronic liver disorder worldwide; mechanisms behind the development and progression of NAFLD and steatohepatitis (NASH) are still debated. Besides, vitamin D is a hormone exerting relevant influence on several metabolic and inflammatory pathways and a direct effect into the liver has been hypothesized and partially proven in both humans and animal models. Recently, knock-out mice for vitamin D receptor (VDR) have been shown to be protected from hepatic fat accumulation. Obesity and adipose tissue (AT) inflammation are major determinants of NAFLD and VDR plays an important immuno-modulating role in AT . Whether a relationship exists between liver expression of VDR in NAFLD/NASH and the presence of visceral AT (VAT) inflammation in obesity has not been investigated yet. Therefore aim of this project is to investigate the hepatic and adipose tissue expression of VDR in obese patients in relation to the presence of NAFLD and VAT inflammation.
Methods. For this purpose VDR expression will be evaluated by immunohistochemistry and real-time PCR in hepatic and omental biopsies from forty obese individuals underwent bariatric surgery. NAFLD will be diagnosed by Brunt definition and graded according to the NAFLD activity score (NAS); fibrosis will be quantified on the basis of the NASH Clinical Research Network Scoring System Definition. VAT inflammation will be determined through IHC and by the analysis of specific genes' expression using rt-PCR.
The clinical implications of the alarming prevalence of NAFLD, the limited knowledge of its underlying pathophysiologic mechanisms and the difficulties in identifying a treatment explain why NAFLD is currently a such important field of research. In this context, the evaluation of the role of vitamin D/VDR system in the aberrant fat accumulation will allow to better understand the processes behind the development of NAFLD and to identify new targets for innovative therapeutic approaches to the management of NAFLD.