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S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803104/ https://www.ncbi.nlm.nih.gov/pubmed/35094654 http://dx.doi.org/10.1080/21623945.2021.2021700 |
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author | Chakrabarty, Sagarika Bui, Quyen Badeanlou, Leylla Hester, Kelly Chun, Jerold Ruf, Wolfram Ciaraldi, Theodore P Samad, Fahumiya |
author_facet | Chakrabarty, Sagarika Bui, Quyen Badeanlou, Leylla Hester, Kelly Chun, Jerold Ruf, Wolfram Ciaraldi, Theodore P Samad, Fahumiya |
author_sort | Chakrabarty, Sagarika |
collection | PubMed |
description | Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects, plasma S1P levels significantly increased in response to the anti-diabetic drug, rosiglitazone, and, S1P levels correlated positively with measures of improved glucose homeostasis. In HFD-induced obese C57BL/6 J mice S1PR3 gene expression was increased in adipose tissues (AT) and liver compared with low fat diet (LFD)-fed counterparts. On a HFD, weight gain was similar in both S1PR3-/- mice and WT littermates; however, HFD-fed S1PR3-/- mice exhibited a phenotype of partial lipodystrophy, exacerbated insulin resistance and glucose intolerance. This worsened metabolic phenotype of HFD-fed S1PR3-/- mice was mechanistically linked with increased adipose inflammation, adipose macrophage and T-cell accumulation, hepatic inflammation and hepatic steatosis. In 3T3-L1 preadipocytes S1P increased adipogenesis and S1P-S1PR3 signalling regulated the expression of PPARγ, suggesting a novel role for this signalling pathway in the adipogenic program. These results reveal an anti-diabetic role for S1P, and, that S1P-S1PR3 signalling in the adipose and liver defends against excessive inflammation and steatosis to maintain metabolic homeostasis at key regulatory pathways. |
format | Online Article Text |
id | pubmed-8803104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-88031042022-02-01 S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction Chakrabarty, Sagarika Bui, Quyen Badeanlou, Leylla Hester, Kelly Chun, Jerold Ruf, Wolfram Ciaraldi, Theodore P Samad, Fahumiya Adipocyte Research Paper Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects, plasma S1P levels significantly increased in response to the anti-diabetic drug, rosiglitazone, and, S1P levels correlated positively with measures of improved glucose homeostasis. In HFD-induced obese C57BL/6 J mice S1PR3 gene expression was increased in adipose tissues (AT) and liver compared with low fat diet (LFD)-fed counterparts. On a HFD, weight gain was similar in both S1PR3-/- mice and WT littermates; however, HFD-fed S1PR3-/- mice exhibited a phenotype of partial lipodystrophy, exacerbated insulin resistance and glucose intolerance. This worsened metabolic phenotype of HFD-fed S1PR3-/- mice was mechanistically linked with increased adipose inflammation, adipose macrophage and T-cell accumulation, hepatic inflammation and hepatic steatosis. In 3T3-L1 preadipocytes S1P increased adipogenesis and S1P-S1PR3 signalling regulated the expression of PPARγ, suggesting a novel role for this signalling pathway in the adipogenic program. These results reveal an anti-diabetic role for S1P, and, that S1P-S1PR3 signalling in the adipose and liver defends against excessive inflammation and steatosis to maintain metabolic homeostasis at key regulatory pathways. Taylor & Francis 2022-01-30 /pmc/articles/PMC8803104/ /pubmed/35094654 http://dx.doi.org/10.1080/21623945.2021.2021700 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Chakrabarty, Sagarika Bui, Quyen Badeanlou, Leylla Hester, Kelly Chun, Jerold Ruf, Wolfram Ciaraldi, Theodore P Samad, Fahumiya S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction |
title | S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction |
title_full | S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction |
title_fullStr | S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction |
title_full_unstemmed | S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction |
title_short | S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction |
title_sort | s1p/s1pr3 signalling axis protects against obesity-induced metabolic dysfunction |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803104/ https://www.ncbi.nlm.nih.gov/pubmed/35094654 http://dx.doi.org/10.1080/21623945.2021.2021700 |
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