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World J Gastroenterol. May 21, 2018; 24(19): 2073-2082
Published online May 21, 2018. doi: 10.3748/wjg.v24.i19.2073
Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease
Lucia Pacifico, Gian Marco Andreoli, Miriam D’Avanzo, Delia De Mitri, Pasquale Pierimarchi
Lucia Pacifico, Gian Marco Andreoli, Miriam D’Avanzo, Delia De Mitri, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome 00161, Italy
Pasquale Pierimarchi, Institute of Translational Pharmacology, National Research Council, Rome 00083, Italy
Author contributions: Pacifico L and Pierimarchi P designed the study, analyzed the data and wrote the manuscript; Andreoli GM, D’Avanzo M, and De Mitri D collected the data; all the authors participated in the critical review and in the final approval of the manuscript.
Conflict-of-interest statement: Authors have no conflicts of interest to disclose.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lucia Pacifico, MD, Associate Professor, Policlinico Umberto I Hospital, Sapienza University of Rome, Viale Regina Elena 324, Rome 00161, Italy. lucia.pacifico@uniroma1.it
Telephone: +39-6-49979215 Fax: +39-6-49979216
Received: March 29, 2018
Peer-review started: March 30, 2018
First decision: April 27, 2018
Revised: May 3, 2018
Accepted: May 11, 2018
Article in press: May 11, 2018
Published online: May 21, 2018
Processing time: 49 Days and 19.1 Hours
Abstract

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.

Keywords: Nonalcoholic fatty liver disease; Insulin resistance; Metabolic syndrome; Osteoprotegerin; Receptor activator of nuclear factor kappa B; Receptor activator of nuclear factor kappa B ligand

Core tip: Recently, epidemiological studies have linked obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG axis activation, has recently been suggested to have critical roles in the initiation and perpetuation of obesity-related comorbidities including NAFLD. The available studies have reported either positive or negative associations between OPG and NAFLD. Thus, more research is needed to clarify its role in this liver disease.