Modulation of Lipid-Induced ER Stress by Fatty Acid Shape
Exposure of pancreatic β cells to long-chain saturated fatty acids (SFA) induces a so-called endoplasmic reticulum (ER) stress that can ultimately lead to cell death. This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in β-cell mass. By cont...
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| Veröffentlicht in: | Traffic (Copenhagen, Denmark) Denmark), 2011-03, Vol.12 (3), p.349-362 |
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| creator | Deguil, Julie Pineau, Ludovic Rowland Snyder, Ellen Claire Dupont, Sébastien Beney, Laurent Gil, Adrià Frapper, Gilles Ferreira, Thierry |
| description | Exposure of pancreatic β cells to long-chain saturated fatty acids (SFA) induces a so-called endoplasmic reticulum (ER) stress that can ultimately lead to cell death. This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in β-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER stress. In the present study, we took advantage of a simple yeast-based model, which brings together most of the trademarks of lipotoxicity in human cells, to screen fatty acids of various structures for their capacity to counter ER stress. Here we demonstrate that the tendency of a free fatty acid (FFA) to reduce SFA toxicity depends on a complex conjunction of parameters, including chain length, level of unsaturation, position of the double bonds and nature of the isomers (cis or trans). Interestingly, potent FFA act as building blocks for phospholipid synthesis and help to restore an optimal membrane organization, compatible with ER function and normal protein trafficking. |
| doi_str_mv | 10.1111/j.1600-0854.2010.01150.x |
| format | Article |
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This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in β-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER stress. In the present study, we took advantage of a simple yeast-based model, which brings together most of the trademarks of lipotoxicity in human cells, to screen fatty acids of various structures for their capacity to counter ER stress. Here we demonstrate that the tendency of a free fatty acid (FFA) to reduce SFA toxicity depends on a complex conjunction of parameters, including chain length, level of unsaturation, position of the double bonds and nature of the isomers (cis or trans). 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This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in β-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER stress. In the present study, we took advantage of a simple yeast-based model, which brings together most of the trademarks of lipotoxicity in human cells, to screen fatty acids of various structures for their capacity to counter ER stress. Here we demonstrate that the tendency of a free fatty acid (FFA) to reduce SFA toxicity depends on a complex conjunction of parameters, including chain length, level of unsaturation, position of the double bonds and nature of the isomers (cis or trans). Interestingly, potent FFA act as building blocks for phospholipid synthesis and help to restore an optimal membrane organization, compatible with ER function and normal protein trafficking.</description><subject>Biochemistry</subject><subject>Biochemistry, Molecular Biology</subject><subject>Cells, Cultured</subject><subject>Cellular Biology</subject><subject>Endoplasmic Reticulum - drug effects</subject><subject>Fatty Acids - chemistry</subject><subject>Fatty Acids - metabolism</subject><subject>Fatty Acids - pharmacology</subject><subject>Fatty Acids, Unsaturated - chemistry</subject><subject>Fatty Acids, Unsaturated - pharmacology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Lipid Bilayers - chemistry</subject><subject>Lipids - chemistry</subject><subject>Lipids - pharmacology</subject><subject>membrane fluidity</subject><subject>Models, Molecular</subject><subject>obesity</subject><subject>Phospholipids - chemistry</subject><subject>Phospholipids - metabolism</subject><subject>PUFA</subject><subject>saturated fatty acids</subject><subject>Stress, Physiological - drug effects</subject><subject>Subcellular Processes</subject><subject>trans fatty acids</subject><subject>type 2 diabetes</subject><subject>UPR</subject><subject>yeast</subject><subject>ω‐3</subject><subject>ω‐6</subject><issn>1398-9219</issn><issn>1600-0854</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtOwzAQRS0EouXxC-Ati4QZ23l4waKqWlqpCKmPtWU7Dk2VNlXSQvP3JAS6ZjYzmrlnFocQiuBjU88bH0MAD-JA-AyaLSAG4J8uSP98uGxmLmNPMpQ9clNVGwBggRDXpMcQBY8w6hP5ViTHXB-yYkeLlM6yfZZ4011ytC6hozldHEpXVdTUdKwPh5oObJbQxVrv3R25SnVeufvffktW49FyOPFm76_T4WDmWSEZeBrTkHMNLkUWMBDcxgYtj4DHKLUwNo6NSQLmEmZcKIwJnLHWIkSRC1IZ8lvy1P1d61zty2yry1oVOlOTwUy1O4AghpDJT2yycZe1ZVFVpUvPAIJqzamNagWpVpBqzakfc-rUoA8duj-arUvO4J-qJvDSBb6y3NX_fqyW80E7Nfxjx6e6UPqjzCq1WjRJDigFRqHg399rgsY</recordid><startdate>201103</startdate><enddate>201103</enddate><creator>Deguil, Julie</creator><creator>Pineau, Ludovic</creator><creator>Rowland Snyder, Ellen Claire</creator><creator>Dupont, Sébastien</creator><creator>Beney, Laurent</creator><creator>Gil, Adrià</creator><creator>Frapper, Gilles</creator><creator>Ferreira, Thierry</creator><general>Blackwell Publishing Ltd</general><general>Wiley</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-3737-3500</orcidid><orcidid>https://orcid.org/0000-0002-2757-2506</orcidid><orcidid>https://orcid.org/0000-0001-5177-6691</orcidid></search><sort><creationdate>201103</creationdate><title>Modulation of Lipid-Induced ER Stress by Fatty Acid Shape</title><author>Deguil, Julie ; Pineau, Ludovic ; Rowland Snyder, Ellen Claire ; Dupont, Sébastien ; Beney, Laurent ; Gil, Adrià ; Frapper, Gilles ; Ferreira, Thierry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4920-a1f633a0ef1252043c8b1c3703819a4bc88bbd52ed2be64bb5ebccc1077e5f963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biochemistry</topic><topic>Biochemistry, Molecular Biology</topic><topic>Cells, Cultured</topic><topic>Cellular Biology</topic><topic>Endoplasmic Reticulum - drug effects</topic><topic>Fatty Acids - chemistry</topic><topic>Fatty Acids - metabolism</topic><topic>Fatty Acids - pharmacology</topic><topic>Fatty Acids, Unsaturated - chemistry</topic><topic>Fatty Acids, Unsaturated - pharmacology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Lipid Bilayers - chemistry</topic><topic>Lipids - chemistry</topic><topic>Lipids - pharmacology</topic><topic>membrane fluidity</topic><topic>Models, Molecular</topic><topic>obesity</topic><topic>Phospholipids - chemistry</topic><topic>Phospholipids - metabolism</topic><topic>PUFA</topic><topic>saturated fatty acids</topic><topic>Stress, Physiological - drug effects</topic><topic>Subcellular Processes</topic><topic>trans fatty acids</topic><topic>type 2 diabetes</topic><topic>UPR</topic><topic>yeast</topic><topic>ω‐3</topic><topic>ω‐6</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Deguil, Julie</creatorcontrib><creatorcontrib>Pineau, Ludovic</creatorcontrib><creatorcontrib>Rowland Snyder, Ellen Claire</creatorcontrib><creatorcontrib>Dupont, Sébastien</creatorcontrib><creatorcontrib>Beney, Laurent</creatorcontrib><creatorcontrib>Gil, Adrià</creatorcontrib><creatorcontrib>Frapper, Gilles</creatorcontrib><creatorcontrib>Ferreira, Thierry</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Traffic (Copenhagen, Denmark)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Deguil, Julie</au><au>Pineau, Ludovic</au><au>Rowland Snyder, Ellen Claire</au><au>Dupont, Sébastien</au><au>Beney, Laurent</au><au>Gil, Adrià</au><au>Frapper, Gilles</au><au>Ferreira, Thierry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of Lipid-Induced ER Stress by Fatty Acid Shape</atitle><jtitle>Traffic (Copenhagen, Denmark)</jtitle><addtitle>Traffic</addtitle><date>2011-03</date><risdate>2011</risdate><volume>12</volume><issue>3</issue><spage>349</spage><epage>362</epage><pages>349-362</pages><issn>1398-9219</issn><eissn>1600-0854</eissn><abstract>Exposure of pancreatic β cells to long-chain saturated fatty acids (SFA) induces a so-called endoplasmic reticulum (ER) stress that can ultimately lead to cell death. This process is believed to participate in insulin deficiency associated with type 2 diabetes, via a decrease in β-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER stress. In the present study, we took advantage of a simple yeast-based model, which brings together most of the trademarks of lipotoxicity in human cells, to screen fatty acids of various structures for their capacity to counter ER stress. Here we demonstrate that the tendency of a free fatty acid (FFA) to reduce SFA toxicity depends on a complex conjunction of parameters, including chain length, level of unsaturation, position of the double bonds and nature of the isomers (cis or trans). 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| ispartof | Traffic (Copenhagen, Denmark), 2011-03, Vol.12 (3), p.349-362 |
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| source | MEDLINE; IngentaConnect Free/Open Access Journals; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Biochemistry Biochemistry, Molecular Biology Cells, Cultured Cellular Biology Endoplasmic Reticulum - drug effects Fatty Acids - chemistry Fatty Acids - metabolism Fatty Acids - pharmacology Fatty Acids, Unsaturated - chemistry Fatty Acids, Unsaturated - pharmacology Humans Life Sciences Lipid Bilayers - chemistry Lipids - chemistry Lipids - pharmacology membrane fluidity Models, Molecular obesity Phospholipids - chemistry Phospholipids - metabolism PUFA saturated fatty acids Stress, Physiological - drug effects Subcellular Processes trans fatty acids type 2 diabetes UPR yeast ω‐3 ω‐6 |
| title | Modulation of Lipid-Induced ER Stress by Fatty Acid Shape |
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