Research progress, challenges and perspectives of phospholipids metabolism in the LXR‑LPCAT3 signaling pathway and its relation to NAFLD (Review)

Wang,Junmin; Li,Jiacheng; Fu,Yugang; Zhu,Yingying; Lin,Liubing; Li,Yong

doi:10.3892/ijmm.2024.5356

Research progress, challenges and perspectives of phospholipids metabolism in the LXR‑LPCAT3 signaling pathway and its relation to NAFLD (Review)

Authors:
- Junmin Wang
- Jiacheng Li
- Yugang Fu
- Yingying Zhu
- Liubing Lin
- Yong Li
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Affiliations: Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, P.R. China
Published online on: February 12, 2024 https://doi.org/10.3892/ijmm.2024.5356
Article Number: 32
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Phospholipids (PLs) are principle constituents of biofilms, with their fatty acyl chain composition significantly impacting the biophysical properties of membranes, thereby influencing biological processes. Recent studies have elucidated that fatty acyl chains, under the enzymatic action of lyso‑phosphatidyl‑choline acyltransferases (LPCATs), expedite incorporation into the sn‑2 site of phosphatidyl‑choline (PC), profoundly affecting pathophysiology. Accumulating evidence suggests that alterations in LPCAT activity are implicated in various diseases, including non‑alcoholic fatty liver disease (NAFLD), hepatitis C, atherosclerosis and cancer. Specifically, LPCAT3 is instrumental in maintaining systemic lipid homeostasis through its roles in hepatic lipogenesis, intestinal lipid absorption and lipoprotein secretion. The liver X receptor (LXR), pivotal in lipid homeostasis, modulates cholesterol, fatty acid (FA) and PL metabolism. LXR's capacity to modify PL composition in response to cellular sterol fluctuations is a vital mechanism for protecting biofilms against lipid stress. Concurrently, LXR activation enhances LPCAT3 expression on cell membranes and elevates polyunsaturated PL levels. This activation can ameliorate saturated free FA effects in vitro or endoplasmic reticulum stress in vivo due to lipid accumulation in hepatic cells. Pharmacological interventions targeting LXR, LPCAT and membrane PL components could offer novel therapeutic directions for NAFLD management. The present review primarily focused on recent advancements in understanding the LPCAT3 signaling pathway's role in lipid metabolism related to NAFLD, aiming to identify new treatment targets for the disease.

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