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World J Gastroenterol. Jun 28, 2019; 25(24): 3009-3020
Published online Jun 28, 2019. doi: 10.3748/wjg.v25.i24.3009
Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease
José M Mato, Cristina Alonso, Mazen Noureddin, Shelly C Lu
José M Mato, CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, Derio 48160, Bizkaia, Spain
Cristina Alonso, OWL Metabolomics, Technology Park of Bizkaia, Derio 48160, Bizkaia, Spain
Mazen Noureddin, Shelly C Lu, Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Author contributions: All authors contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Open-Access: This is an open-access article that 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/
Corresponding author: José M Mato, PhD, Director, Professor, CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology Park of Bizkaia, Derio 48160, Bizkaia, Spain. director@cicbiogune.es
Telephone: +34-946-572517 Fax: +34-944-061-301
Received: March 22, 2019
Peer-review started: March 22, 2019
First decision: April 11, 2019
Revised: May 6, 2019
Accepted: May 18, 2019
Article in press: May 18, 2019
Published online: June 28, 2019
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy. NAFLD covers a spectrum that ranges from simple steatosis, nonalcoholic steatohepatitis (NASH) with varying degrees of fibrosis, to cirrhosis, which is a major risk factor for hepatocellular carcinoma. Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity, type 2 diabetes mellitus and dyslipidemia, with a global prevalence of 25%. NAFLD arises when the uptake of fatty acids (FA) and triglycerides (TG) from circulation and de novo lipogenesis saturate the rate of FA β-oxidation and very-low density lipoprotein (VLDL)-TG export. Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH, and therefore, alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression. This review focuses on the importance of the classification of NAFLD patients into different subtypes, corresponding to the main alteration(s) in the major pathways that regulate FA homeostasis leading, in each case, to the initiation and progression of NASH. This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments.

Keywords: S-adenosylmethionine, Methionine adenosyltransferase, Lipid metabolism, Multiomics, Lipidomics, Nonalcoholic steatohepatitis, One-carbon metabolism, Very low-density lipoproteins, Steatosis, Precision medicine

Core tip: Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy. The advent of metabolomics has shown that NAFLD progression from simple steatosis to nonalcoholic steatohepatitis (NASH) associates with profound alterations in liver and serum lipidomic signatures that are good indicators of the disease’s development and progression. Lipidomics has also permitted the classification of NAFLD patients into different subtypes corresponding to the main alteration(s) leading, in each case, to the initiation and progression of NASH based on the identification of specific lipid signatures, opening the door to the development of precise NASH treatments.