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World J Gastroenterol. Mar 14, 2015; 21(10): 2875-2882
Published online Mar 14, 2015. doi: 10.3748/wjg.v21.i10.2875
Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease: The search for alternative causative factors
Jordi Camps, Jorge Joven
Jordi Camps, Jorge Joven, Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain
Author contributions: Both authors contributed equally to the interpretation and acquisition of data and the writing and approval of the manuscript.
Supported by Instituto de Salud Carlos III, No. PI08/1381, and No. PI11/00130; Carlos III Health Institute, Madrid, Spain; and the Fondo Europeo de Desarrollo Regional.
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: Jorge Joven, MD, PhD, Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, c/ Sant Llorenç 21, 43201 Reus, Spain. jorge.joven@urv.cat
Telephone: +34-97-7310300 Fax: +34-97-759386
Received: July 14, 2014
Peer-review started: July 15, 2014
First decision: August 15, 2014
Revised: September 2, 2014
Accepted: September 29, 2014
Article in press: September 30, 2014
Published online: March 14, 2015
Processing time: 244 Days and 21.3 Hours
Abstract

The incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is constantly increasing. Despite this is apparently associated with the growing increase in obesity, insulin resistance and obesity-related metabolic disturbances their presence is not a necessary or sufficient condition to explain the accumulation of fat in the liver. Conversely, NAFLD is a predictor of other metabolic risks. NAFLD is currently the most frequent chronic liver disease but should not be considered benign or anecdotic because a considerable proportion of patients with NAFLD progress to cirrhosis and end-stage liver disease. Consequently, the search for alternative molecular mechanisms with therapeutic implications in NAFLD and associated disorders deserves a careful consideration. Mitochondria are possible targets as these organelles generate energy from nutrient oxidation. Some findings, generated in patients with extreme obesity and in murine models, support the notion that NAFLD could be a mitochondrial disease. This is plausible because mitochondrial dysfunction affects the accumulation of lipids in hepatocytes and promotes lipid peroxidation, the production of reactive oxygen species, the release of cytokines causing inflammation and cell death. Here we discuss basic research and mechanistic studies targeting the role of chemokine ligand 2 in liver inflammation and that of the paraoxonases in the oxidative stress. Their combination and association with mitochondrial dysfunction may uncover mechanisms underlying the progression of NAFLD and may help to identify novel therapeutic targets.

Keywords: Biomarkers; Cytokines; Inflammation; Metabolism; Mitochondrial dysfunction; Metabolic profiling; Obesity; Oxidation; Risk factors

Core tip: Recently acquired knowledge on the role of oxidation, inflammation and mitochondrial dysfunction in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) suggests a crucial role in the search for biological markers and therapeutic targets to alleviate the progression of the disease. Classically associated with obesity, the pathogenesis of NAFLD is extremely complex and mostly unknown. Consequently, the correct clinical management and prevention has not been established yet. Despite disparate results in the literature, mainly due to the different methods to measure the oxidative stress, there is currently no doubt that oxidative stress plays a crucial role. Similarly, the infiltration of monocytes, mainly due to the action of chemokines, is a relevant factor. However, to uncover the actual molecular mechanisms has proven to be more difficult than expected. The role of both oxidation and inflammation could be considered defensive and/or causative but the combination of these and other mechanisms may improve the understanding of NAFLD as a manifestation of mitochondrial disease. J. Camps and J. Joven. Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease: the search for alternative causative factors.