Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2018; 24(36): 4132-4151
Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4132
Production of extracellular lysophosphatidic acid in the regulation of adipocyte functions and liver fibrosis
Fang Yang, Guo-Xun Chen
Fang Yang, School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, Hubei Province, China
Guo-Xun Chen, Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, United States
Author contributions: Yang F searched the publications, summarized data in tables, drew figures, discussed the literature and wrote the review; Chen GX designed the structure of the review and modified the review; all authors approved the final version of this review.
Supported by the National Natural Science Foundation of China, No. 31401510.
Conflict-of-interest statement: We declare that we have no conflicts of interest.
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: Guo-Xun Chen, MD, PhD, Associate Professor, Research Scientist, Department of Nutrition, University of Tennessee at Knoxville, Room 229, Jessie Harris Building, 1215 West Cumberland Avenue, Knoxville, TN 37996, United States. gchen6@utk.edu
Telephone: +1-865-9746254 Fax: +1-865-9743491
Received: March 24, 2018
Peer-review started: March 25, 2018
First decision: April 18, 2018
Revised: April 24, 2018
Accepted: May 6, 2018
Article in press: May 6, 2018
Published online: September 28, 2018
Processing time: 185 Days and 0.3 Hours
Abstract

Lysophosphatidic acid (LPA), a glycerophospholipid, consists of a glycerol backbone connected to a phosphate head group and an acyl chain linked to sn-1 or sn-2 position. In the circulation, LPA is in sub-millimolar range and mainly derived from hydrolysis of lysophosphatidylcholine, a process mediated by lysophospholipase D activity in proteins such as autotaxin (ATX). Intracellular and extracellular LPAs act as bioactive lipid mediators with diverse functions in almost every mammalian cell type. The binding of LPA to its receptors LPA1-6 activates multiple cellular processes such as migration, proliferation and survival. The production of LPA and activation of LPA receptor signaling pathways in the events of physiology and pathophysiology have attracted the interest of researchers. Results from studies using transgenic and gene knockout animals with alterations of ATX and LPA receptors genes, have revealed the roles of LPA signaling pathways in metabolic active tissues and organs. The present review was aimed to summarize recent progresses in the studies of extracellular and intracellular LPA production pathways. This includes the functional, structural and biochemical properties of ATX and LPA receptors. The potential roles of LPA production and LPA receptor signaling pathways in obesity, insulin resistance and liver fibrosis are also discussed.

Keywords: Autotaxin; Lysophosphatidic acid receptors; Obesity; Lysophosphatidic acid; Insulin resistance; Liver fibrosis

Core tip: Lysophosphatidic acid (LPA) is mainly derived from hydrolysis of lysophosphatidylcholine, a process mediated by lysophospholipase D activity in proteins such as autotaxin (ATX). The binding of LPA to its receptors LPA1-6 activates multiple cellular signaling pathways and leads to changes. Studies using genetically modified animals have begun to reveal the roles of LPA pathways in metabolic active tissues and organs. The present review summarized recent progresses in the studies of extracellular and intracellular LPA production pathways; the functions, structural and biochemical properties of ATX and LPA receptors. Furthermore, the potential roles of LPA production and LPA receptor signaling pathways in obesity, insulin resistance and liver fibrosis are discussed.