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Cited by 192

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Saturated Fatty Acids Engage an IRE1α-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells

Open access
Robblee, Megan M., Kim, Charles C., Abate, Jess Porter, Valdearcos, Martin, Sandlund, Karin L.M., Shenoy, Meera K., Volmer, Romain, Iwawaki, Takao, Koliwad, Suneil K.·2016·Cell Reports

Abstract

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.

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Crossref · 10.1016/j.celrep.2016.02.053

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Metadata

Authors
Robblee, M. M., Kim, C. C., Abate, J. P., Valdearcos, M., Sandlund, K. L. M., Shenoy, M. K., Volmer, R., Iwawaki, T., & Koliwad, S. K.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2016-03
Volume
14
Issue
11
Pages
2611-2623
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2294248185
Cited by
192
References
9
FWCI
10.83
Type
journal article
Language
en
Open access
gold

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