Ectopic fat accumulation in human astrocytes impairs insulin action
Astrocytes provide neurons with structural support and energy in form of lactate, modulate synaptic transmission, are insulin sensitive and act as gatekeeper for water, ions, glutamate and second messengers. Furthermore, astrocytes are important for glucose sensing, possess neuroendocrine functions...
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The Royal Society
2020-09-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.200701 |
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| author | Martin Heni Sabine S. Eckstein Jens Schittenhelm Anja Böhm Norbert Hogrefe Martin Irmler Johannes Beckers Martin Hrabě de Angelis Hans-Ulrich Häring Andreas Fritsche Harald Staiger |
| author_facet | Martin Heni Sabine S. Eckstein Jens Schittenhelm Anja Böhm Norbert Hogrefe Martin Irmler Johannes Beckers Martin Hrabě de Angelis Hans-Ulrich Häring Andreas Fritsche Harald Staiger |
| author_sort | Martin Heni |
| collection | DOAJ |
| description | Astrocytes provide neurons with structural support and energy in form of lactate, modulate synaptic transmission, are insulin sensitive and act as gatekeeper for water, ions, glutamate and second messengers. Furthermore, astrocytes are important for glucose sensing, possess neuroendocrine functions and also play an important role in cerebral lipid metabolism. To answer the question, if there is a connection between lipid metabolism and insulin action in human astrocytes, we investigated if storage of ectopic lipids in human astrocytes has an impact on insulin signalling in those cells. Human astrocytes were cultured in the presence of a lipid emulsion, consisting of fatty acids and triglycerides, to induce ectopic lipid storage. After several days, cells were stimulated with insulin and gene expression profiling was performed. In addition, phosphorylation of Akt as well as glycogen synthesis and cell proliferation was assessed. Ectopic lipid storage was detected in human astrocytes after lipid exposure and lipid storage was persistent even when the fat emulsion was removed from the cell culture medium. Chronic exposure to lipids induced profound changes in the gene expression profile, whereby some genes showed a reversible gene expression profile upon removal of fat, and some did not. This included FOXO-dependent expression patterns. Furthermore, insulin-induced phosphorylation of Akt was diminished and also insulin-induced glycogen synthesis and proliferation was impaired in lipid-laden astrocytes. Chronic lipid exposure induces lipid storage in human astrocytes accompanied by insulin resistance. Analyses of the gene expression pattern indicated the potential of a partially reversible gene expression profile. Targeting astrocytic insulin resistance by reducing ectopic lipid load might represent a promising treatment target for insulin resistance of the brain in obesity, diabetes and neurodegeneration. |
| format | Article |
| id | doaj-art-998f7a345f3d43b09fb65dec017af0d7 |
| institution | OA Journals |
| issn | 2054-5703 |
| language | English |
| publishDate | 2020-09-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj-art-998f7a345f3d43b09fb65dec017af0d72025-08-20T02:11:58ZengThe Royal SocietyRoyal Society Open Science2054-57032020-09-017910.1098/rsos.200701Ectopic fat accumulation in human astrocytes impairs insulin actionMartin Heni0Sabine S. Eckstein1Jens Schittenhelm2Anja Böhm3Norbert Hogrefe4Martin Irmler5Johannes Beckers6Martin Hrabě de Angelis7Hans-Ulrich Häring8Andreas Fritsche9Harald Staiger10Department of Internal Medicine, Division of Endocrinology, Diabetology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyDivision of Neuropathology, University Hospital Tübingen, Tübingen, GermanyDepartment of Internal Medicine, Division of Endocrinology, Diabetology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyDepartment of Physiology, University of Bern, Bern, SwitzerlandInstitute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyDepartment of Internal Medicine, Division of Endocrinology, Diabetology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyDepartment of Internal Medicine, Division of Endocrinology, Diabetology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, GermanyAstrocytes provide neurons with structural support and energy in form of lactate, modulate synaptic transmission, are insulin sensitive and act as gatekeeper for water, ions, glutamate and second messengers. Furthermore, astrocytes are important for glucose sensing, possess neuroendocrine functions and also play an important role in cerebral lipid metabolism. To answer the question, if there is a connection between lipid metabolism and insulin action in human astrocytes, we investigated if storage of ectopic lipids in human astrocytes has an impact on insulin signalling in those cells. Human astrocytes were cultured in the presence of a lipid emulsion, consisting of fatty acids and triglycerides, to induce ectopic lipid storage. After several days, cells were stimulated with insulin and gene expression profiling was performed. In addition, phosphorylation of Akt as well as glycogen synthesis and cell proliferation was assessed. Ectopic lipid storage was detected in human astrocytes after lipid exposure and lipid storage was persistent even when the fat emulsion was removed from the cell culture medium. Chronic exposure to lipids induced profound changes in the gene expression profile, whereby some genes showed a reversible gene expression profile upon removal of fat, and some did not. This included FOXO-dependent expression patterns. Furthermore, insulin-induced phosphorylation of Akt was diminished and also insulin-induced glycogen synthesis and proliferation was impaired in lipid-laden astrocytes. Chronic lipid exposure induces lipid storage in human astrocytes accompanied by insulin resistance. Analyses of the gene expression pattern indicated the potential of a partially reversible gene expression profile. Targeting astrocytic insulin resistance by reducing ectopic lipid load might represent a promising treatment target for insulin resistance of the brain in obesity, diabetes and neurodegeneration.https://royalsocietypublishing.org/doi/10.1098/rsos.200701astrocytehumaninsulinlipid storage |
| spellingShingle | Martin Heni Sabine S. Eckstein Jens Schittenhelm Anja Böhm Norbert Hogrefe Martin Irmler Johannes Beckers Martin Hrabě de Angelis Hans-Ulrich Häring Andreas Fritsche Harald Staiger Ectopic fat accumulation in human astrocytes impairs insulin action Royal Society Open Science astrocyte human insulin lipid storage |
| title | Ectopic fat accumulation in human astrocytes impairs insulin action |
| title_full | Ectopic fat accumulation in human astrocytes impairs insulin action |
| title_fullStr | Ectopic fat accumulation in human astrocytes impairs insulin action |
| title_full_unstemmed | Ectopic fat accumulation in human astrocytes impairs insulin action |
| title_short | Ectopic fat accumulation in human astrocytes impairs insulin action |
| title_sort | ectopic fat accumulation in human astrocytes impairs insulin action |
| topic | astrocyte human insulin lipid storage |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.200701 |
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