Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells
Diets rich in saturated fatty acids (SFAs) produce a form of tissue inflammation driven by “metabolically activated” macrophages. We show that SFAs, when in excess, induce a unique transcriptional signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, partic...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716301747 |
| _version_ | 1818990403384246272 |
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| author | Megan M. Robblee Charles C. Kim Jess Porter Abate Martin Valdearcos Karin L.M. Sandlund Meera K. Shenoy Romain Volmer Takao Iwawaki Suneil K. Koliwad |
| author_facet | Megan M. Robblee Charles C. Kim Jess Porter Abate Martin Valdearcos Karin L.M. Sandlund Meera K. Shenoy Romain Volmer Takao Iwawaki Suneil K. Koliwad |
| author_sort | Megan M. Robblee |
| collection | DOAJ |
| description | Diets rich in saturated fatty acids (SFAs) produce a form of tissue inflammation driven by “metabolically activated” macrophages. We show that SFAs, when in excess, induce a unique transcriptional signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, particularly IRE1α and many adaptive downstream target genes. SFAs also activate the NLRP3 inflammasome in macrophages, resulting in IL-1β secretion. We found that IRE1α mediates SFA-induced IL-1β secretion by macrophages and that its activation by SFAs does not rely on unfolded protein sensing. We show instead that the ability of SFAs to stimulate either IRE1α activation or IL-1β secretion can be specifically reduced by preventing their flux into phosphatidylcholine (PC) or by increasing unsaturated PC levels. Thus, IRE1α is an unrecognized intracellular PC sensor critical to the process by which SFAs stimulate macrophages to secrete IL-1β, a driver of diet-induced tissue inflammation. |
| first_indexed | 2024-12-20T19:53:49Z |
| format | Article |
| id | doaj.art-70a99a0354464db5bc5d7b1b33d1d262 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T19:53:49Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-70a99a0354464db5bc5d7b1b33d1d2622022-12-21T19:28:13ZengElsevierCell Reports2211-12472016-03-0114112611262310.1016/j.celrep.2016.02.053Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid CellsMegan M. Robblee0Charles C. Kim1Jess Porter Abate2Martin Valdearcos3Karin L.M. Sandlund4Meera K. Shenoy5Romain Volmer6Takao Iwawaki7Suneil K. Koliwad8Diabetes Center, University of California San Francisco, San Francisco, CA 94143, USADepartment of Medicine, University of California San Francisco, San Francisco, CA 94143, USADiabetes Center, University of California San Francisco, San Francisco, CA 94143, USADiabetes Center, University of California San Francisco, San Francisco, CA 94143, USADiabetes Center, University of California San Francisco, San Francisco, CA 94143, USADiabetes Center, University of California San Francisco, San Francisco, CA 94143, USAUniversite de Toulouse, INP, ENVT, UMR1225, IHAP, 31076 Toulouse, FranceEducation and Research Support Center, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, JapanDiabetes Center, University of California San Francisco, San Francisco, CA 94143, USADiets rich in saturated fatty acids (SFAs) produce a form of tissue inflammation driven by “metabolically activated” macrophages. We show that SFAs, when in excess, induce a unique transcriptional signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, particularly IRE1α and many adaptive downstream target genes. SFAs also activate the NLRP3 inflammasome in macrophages, resulting in IL-1β secretion. We found that IRE1α mediates SFA-induced IL-1β secretion by macrophages and that its activation by SFAs does not rely on unfolded protein sensing. We show instead that the ability of SFAs to stimulate either IRE1α activation or IL-1β secretion can be specifically reduced by preventing their flux into phosphatidylcholine (PC) or by increasing unsaturated PC levels. Thus, IRE1α is an unrecognized intracellular PC sensor critical to the process by which SFAs stimulate macrophages to secrete IL-1β, a driver of diet-induced tissue inflammation.http://www.sciencedirect.com/science/article/pii/S2211124716301747 |
| spellingShingle | Megan M. Robblee Charles C. Kim Jess Porter Abate Martin Valdearcos Karin L.M. Sandlund Meera K. Shenoy Romain Volmer Takao Iwawaki Suneil K. Koliwad Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells Cell Reports |
| title | Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells |
| title_full | Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells |
| title_fullStr | Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells |
| title_full_unstemmed | Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells |
| title_short | Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells |
| title_sort | saturated fatty acids engage an ire1α dependent pathway to activate the nlrp3 inflammasome in myeloid cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716301747 |
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