Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2021; 13(11): 1512-1533
Published online Nov 27, 2021. doi: 10.4254/wjh.v13.i11.1512
Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis
Yunxia Ma, Miljana Nenkov, Yuan Chen, Adrian T Press, Elke Kaemmerer, Nikolaus Gassler
Yunxia Ma, Miljana Nenkov, Yuan Chen, Nikolaus Gassler, Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Jena 07747, Germany
Adrian T Press, Department of Anesthesiology and Intensive Care Medicine and Center for Sepsis Control and Care, Jena University Hospital, Friedrich Schiller University Jena, Jena 07747, Germany
Elke Kaemmerer, Department of Pediatrics, Jena University Hospital, Friedrich Schiller University Jena, Jena 07747, Germany
Author contributions: Gassler N conceived the concept and also contributed to the correction; Nenkov M and Ma Y wrote the manuscript; Chen Y wrote the abstract and core tips, and modified the review; Press A and Kaemmerer E critically reviewed the manuscript.
Supported by the Interdisziplinäres Zentrum für Klinische Forschung (IZKF-MSP-06) of University Hospital Jena.
Conflict-of-interest statement: Authors declare no conflict of interests for this article
Open-Access: This article 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 NonCommercial (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: Nikolaus Gassler, MA, MD, Professor, Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, Jena 07747, Germany. nikolaus.gassler@med.uni-jena.de
Received: February 25, 2021
Peer-review started: February 25, 2021
First decision: June 15, 2021
Revised: June 28, 2021
Accepted: October 11, 2021
Article in press: October 11, 2021
Published online: November 27, 2021
Abstract

Fatty acids are energy substrates and cell components which participate in regulating signal transduction, transcription factor activity and secretion of bioactive lipid mediators. The acyl-CoA synthetases (ACSs) family containing 26 family members exhibits tissue-specific distribution, distinct fatty acid substrate preferences and diverse biological functions. Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis, designated as the bidirectional relationship between the gut, microbiome and liver, is closely associated with a range of human diseases including metabolic disorders, inflammatory disease and carcinoma in the gastrointestinal tract and liver. In this review, we depict the role of ACSs in fatty acid metabolism, possible molecular mechanisms through which they exert functions, and their involvement in hepatocellular and colorectal carcinoma, with particular attention paid to long-chain fatty acids and small-chain fatty acids. Additionally, the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed. Moreover, the development of potentially therapeutic small molecules, proteins and compounds targeting ACSs in cancer treatment is summarized.

Keywords: Long-chain fatty acids, Short-chain fatty acids, Acyl-CoA synthetases, Microbiota, Liver-gut axis

Core Tip: To understand the role of acyl-CoA synthetases (ACSs) in the fatty acid metabolism, it is necessary to explore the biological function, gene interactions/ regulations and signal pathways in physiological and pathological conditions. Growing evidence demonstrates that the control of microbial balance plays an important role in maintaining homeostasis and normal functions of the liver-gut axis, and the bidirectional communication in turn affects microbial communities. As novel therapeutic targets, miRNAs are receiving more and more attention, together with other compounds targeting ACSs.