Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes
Obesity is a pathophysiological condition where excess free fatty acids (FFA) target and promote the dysfunctioning of insulin sensitive tissues and of pancreatic β cells. This leads to the dysregulation of glucose homeostasis, which culminates in the onset of type 2 diabetes (T2D). FFA, which accum...
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MDPI AG
2020-07-01
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| author | Jeanne Guitton Cécile L. Bandet Mohamed L. Mariko Sophie Tan-Chen Olivier Bourron Yacir Benomar Eric Hajduch Hervé Le Stunff |
| author_facet | Jeanne Guitton Cécile L. Bandet Mohamed L. Mariko Sophie Tan-Chen Olivier Bourron Yacir Benomar Eric Hajduch Hervé Le Stunff |
| author_sort | Jeanne Guitton |
| collection | DOAJ |
| description | Obesity is a pathophysiological condition where excess free fatty acids (FFA) target and promote the dysfunctioning of insulin sensitive tissues and of pancreatic β cells. This leads to the dysregulation of glucose homeostasis, which culminates in the onset of type 2 diabetes (T2D). FFA, which accumulate in these tissues, are metabolized as lipid derivatives such as ceramide, and the ectopic accumulation of the latter has been shown to lead to lipotoxicity. Ceramide is an active lipid that inhibits the insulin signaling pathway as well as inducing pancreatic β cell death. In mammals, ceramide is a key lipid intermediate for sphingolipid metabolism as is sphingosine-1-phosphate (S1P). S1P levels have also been associated with the development of obesity and T2D. In this review, the current knowledge on S1P metabolism in regulating insulin signaling in pancreatic β cell fate and in the regulation of feeding by the hypothalamus in the context of obesity and T2D is summarized. It demonstrates that S1P can display opposite effects on insulin sensitive tissues and pancreatic β cells, which depends on its origin or its degradation pathway. |
| first_indexed | 2024-03-10T18:30:19Z |
| format | Article |
| id | doaj.art-2ab8398c59284279b40f87c07b2f11ce |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:30:19Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2ab8398c59284279b40f87c07b2f11ce2023-11-20T06:38:02ZengMDPI AGCells2073-44092020-07-0197168210.3390/cells9071682Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 DiabetesJeanne Guitton0Cécile L. Bandet1Mohamed L. Mariko2Sophie Tan-Chen3Olivier Bourron4Yacir Benomar5Eric Hajduch6Hervé Le Stunff7Institut des Neurosciences Paris-Saclay, Université Paris Saclay, CNRS UMR 9197, F-91190 Orsay, FranceCentre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, FranceInstitut des Neurosciences Paris-Saclay, Université Paris Saclay, CNRS UMR 9197, F-91190 Orsay, FranceCentre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, FranceCentre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, FranceInstitut des Neurosciences Paris-Saclay, Université Paris Saclay, CNRS UMR 9197, F-91190 Orsay, FranceCentre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, F-75006 Paris, FranceInstitut des Neurosciences Paris-Saclay, Université Paris Saclay, CNRS UMR 9197, F-91190 Orsay, FranceObesity is a pathophysiological condition where excess free fatty acids (FFA) target and promote the dysfunctioning of insulin sensitive tissues and of pancreatic β cells. This leads to the dysregulation of glucose homeostasis, which culminates in the onset of type 2 diabetes (T2D). FFA, which accumulate in these tissues, are metabolized as lipid derivatives such as ceramide, and the ectopic accumulation of the latter has been shown to lead to lipotoxicity. Ceramide is an active lipid that inhibits the insulin signaling pathway as well as inducing pancreatic β cell death. In mammals, ceramide is a key lipid intermediate for sphingolipid metabolism as is sphingosine-1-phosphate (S1P). S1P levels have also been associated with the development of obesity and T2D. In this review, the current knowledge on S1P metabolism in regulating insulin signaling in pancreatic β cell fate and in the regulation of feeding by the hypothalamus in the context of obesity and T2D is summarized. It demonstrates that S1P can display opposite effects on insulin sensitive tissues and pancreatic β cells, which depends on its origin or its degradation pathway.https://www.mdpi.com/2073-4409/9/7/1682Sphingosine-1-phosphateobesitytype 2 diabetesinsulin resistancepancreatic β cell fatehypothalamus |
| spellingShingle | Jeanne Guitton Cécile L. Bandet Mohamed L. Mariko Sophie Tan-Chen Olivier Bourron Yacir Benomar Eric Hajduch Hervé Le Stunff Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes Cells Sphingosine-1-phosphate obesity type 2 diabetes insulin resistance pancreatic β cell fate hypothalamus |
| title | Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes |
| title_full | Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes |
| title_fullStr | Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes |
| title_full_unstemmed | Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes |
| title_short | Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes |
| title_sort | sphingosine 1 phosphate metabolism in the regulation of obesity type 2 diabetes |
| topic | Sphingosine-1-phosphate obesity type 2 diabetes insulin resistance pancreatic β cell fate hypothalamus |
| url | https://www.mdpi.com/2073-4409/9/7/1682 |
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