Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2017; 23(19): 3407-3417
Published online May 21, 2017. doi: 10.3748/wjg.v23.i19.3407
Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease
Flavia A Cimini, Ilaria Barchetta, Simone Carotti, Laura Bertoccini, Marco G Baroni, Umberto Vespasiani-Gentilucci, Maria-Gisella Cavallo, Sergio Morini
Flavia A Cimini, Ilaria Barchetta, Maria-Gisella Cavallo, Laura Bertoccini, Marco G Baroni, Department of Experimental Medicine, Sapienza University of Rome, 00128 Rome, Italy
Simone Carotti, Sergio Morini, Laboratory of Microscopic and Ultrastructural Anatomy (CIR), Faculty of Medicine, University Campus Bio-Medico, 00128 Rome, Italy
Umberto Vespasiani-Gentilucci, Internal Medicine and Hepatology, University Campus Bio-Medico, 00128 Rome, Italy
Author contributions: Cimini FA, Barchetta I, Carotti S, Bertoccini L and Vespasiani-Gentilucci U contributed to the literature review and wrote the paper; Baroni MG, Cavallo MG and Morini S contributed to the study conception, made revisions and helped with writing.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Sergio Morini, MD, Professor, Laboratory of Microscopic and Ultrastructural Anatomy (CIR), Faculty of Medicine, University Campus Bio-Medico, Via Alvaro Del Portillo, 21, 00128 Rome, Italy.
Telephone: +39-06-225419170 Fax: +39-06-22541456
Received: December 24, 2016
Peer-review started: December 28, 2016
First decision: February 9, 2017
Revised: February 28, 2017
Accepted: April 13, 2017
Article in press: April 13, 2017
Published online: May 21, 2017

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Its pathogenesis is complex and not yet fully understood. Over the years many studies have proposed various pathophysiological hypotheses, among which the currently most widely accepted is the “multiple parallel hits” theory. According to this model, lipid accumulation in the hepatocytes and insulin resistance increase the vulnerability of the liver to many factors that act in a coordinated and cooperative manner to promote hepatic injury, inflammation and fibrosis. Among these factors, adipose tissue dysfunction and subsequent chronic low grade inflammation play a crucial role. Recent studies have shown that vitamin D exerts an immune-regulating action on adipose tissue, and the growing wealth of epidemiological data is demonstrating that hypovitaminosis D is associated with both obesity and NAFLD. Furthermore, given the strong association between these conditions, current findings suggest that vitamin D may be involved in the relationship between adipose tissue dysfunction and NAFLD. The purpose of this review is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to adipose tissue dysfunction, and in the pathophysiology linking vitamin D deficiency with NAFLD and adiposity, together with an overview of the evidence available on the clinical utility of vitamin D supplementation in cases of NAFLD.

Keywords: Adipose tissue dysfunction, Vitamin D, Non-alcoholic fatty liver disease, Steatosis, Non-alcoholic steatohepatitis, Obesity, Adipokines

Core tip: Obesity-associated chronic low-grade inflammation plays a pivotal role in the development of non-alcoholic fatty liver disease (NAFLD). Vitamin D deficiency is associated with both obesity and NAFLD, and its anti-inflammatory and immune-modulatory properties provided plausible mechanisms by which hypovitaminosis D may link adipose tissue dysfunction and NAFLD. Animal studies showed beneficial effect of vitamin D supplementation on systemic inflammation and NAFLD, but these data are not confirmed by the results of clinical trials so far conducted in humans.