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Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease

Two decades ago, sphingosine 1-phosphate (S1P) was discovered as a novel bioactive molecule that regulates a variety of cellular functions. The plethora of S1P-mediated effects is due to the fact that the sphingolipid not only modulates intracellular functions but also acts as a ligand of G protein-...

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Autor principal: Kleuser, Burkhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877583/
https://www.ncbi.nlm.nih.gov/pubmed/29510489
http://dx.doi.org/10.3390/ijms19030722
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author Kleuser, Burkhard
author_facet Kleuser, Burkhard
author_sort Kleuser, Burkhard
collection PubMed
description Two decades ago, sphingosine 1-phosphate (S1P) was discovered as a novel bioactive molecule that regulates a variety of cellular functions. The plethora of S1P-mediated effects is due to the fact that the sphingolipid not only modulates intracellular functions but also acts as a ligand of G protein-coupled receptors after secretion into the extracellular environment. In the plasma, S1P is found in high concentrations, modulating immune cell trafficking and vascular endothelial integrity. The liver is engaged in modulating the plasma S1P content, as it produces apolipoprotein M, which is a chaperone for the S1P transport. Moreover, the liver plays a substantial role in glucose and lipid homeostasis. A dysfunction of glucose and lipid metabolism is connected with the development of liver diseases such as hepatic insulin resistance, non-alcoholic fatty liver disease, or liver fibrosis. Recent studies indicate that S1P is involved in liver pathophysiology and contributes to the development of liver diseases. In this review, the current state of knowledge about S1P and its signaling in the liver is summarized with a specific focus on the dysregulation of S1P signaling in obesity-mediated liver diseases. Thus, the modulation of S1P signaling can be considered as a potential therapeutic target for the treatment of hepatic diseases.
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spelling pubmed-58775832018-04-09 Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease Kleuser, Burkhard Int J Mol Sci Review Two decades ago, sphingosine 1-phosphate (S1P) was discovered as a novel bioactive molecule that regulates a variety of cellular functions. The plethora of S1P-mediated effects is due to the fact that the sphingolipid not only modulates intracellular functions but also acts as a ligand of G protein-coupled receptors after secretion into the extracellular environment. In the plasma, S1P is found in high concentrations, modulating immune cell trafficking and vascular endothelial integrity. The liver is engaged in modulating the plasma S1P content, as it produces apolipoprotein M, which is a chaperone for the S1P transport. Moreover, the liver plays a substantial role in glucose and lipid homeostasis. A dysfunction of glucose and lipid metabolism is connected with the development of liver diseases such as hepatic insulin resistance, non-alcoholic fatty liver disease, or liver fibrosis. Recent studies indicate that S1P is involved in liver pathophysiology and contributes to the development of liver diseases. In this review, the current state of knowledge about S1P and its signaling in the liver is summarized with a specific focus on the dysregulation of S1P signaling in obesity-mediated liver diseases. Thus, the modulation of S1P signaling can be considered as a potential therapeutic target for the treatment of hepatic diseases. MDPI 2018-03-03 /pmc/articles/PMC5877583/ /pubmed/29510489 http://dx.doi.org/10.3390/ijms19030722 Text en © 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kleuser, Burkhard
Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease
title Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease
title_full Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease
title_fullStr Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease
title_full_unstemmed Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease
title_short Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease
title_sort divergent role of sphingosine 1-phosphate in liver health and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877583/
https://www.ncbi.nlm.nih.gov/pubmed/29510489
http://dx.doi.org/10.3390/ijms19030722
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