FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches to comprehensively assess the diverse FFAs circulating in human plasma. Furthermore, assessing how FFA-mediated processes interact with genetic risk for disease remains elusive. Here, we report the design and implementation of fatty acid library for comprehensive ontologies (FALCON), an unbiased, scalable, and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids associated with decreased membrane fluidity. Furthermore, we prioritized genes that reflect the combined effects of harmful FFA exposure and genetic risk for type 2 diabetes (T2D). We found that c-MAF-inducing protein (CMIP) protects cells from FFA exposure by modulating Akt signaling. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Cell metabolism - 35(2023), 5 vom: 02. Mai, Seite 887-905.e11 |
| Sprache: |
Englisch |
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| Links: |
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Date Completed 05.05.2023 Date Revised 13.02.2024 published: Print-Electronic UpdateOf: bioRxiv. 2023 Feb 20;:. - PMID 36865221 Citation Status MEDLINE |
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| doi: |
10.1016/j.cmet.2023.03.018 |
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NLM355795876 |
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| 100 | 1 | |a Wieder, Nicolas |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a UpdateOf: bioRxiv. 2023 Feb 20;:. - PMID 36865221 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches to comprehensively assess the diverse FFAs circulating in human plasma. Furthermore, assessing how FFA-mediated processes interact with genetic risk for disease remains elusive. Here, we report the design and implementation of fatty acid library for comprehensive ontologies (FALCON), an unbiased, scalable, and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids associated with decreased membrane fluidity. Furthermore, we prioritized genes that reflect the combined effects of harmful FFA exposure and genetic risk for type 2 diabetes (T2D). We found that c-MAF-inducing protein (CMIP) protects cells from FFA exposure by modulating Akt signaling. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CMIP | |
| 650 | 4 | |a GWAS | |
| 650 | 4 | |a erucic acid | |
| 650 | 4 | |a kidney | |
| 650 | 4 | |a lipidomics | |
| 650 | 4 | |a microglia | |
| 650 | 4 | |a obesity | |
| 650 | 4 | |a pancreatic β cell | |
| 650 | 4 | |a transcriptomics | |
| 650 | 4 | |a type 2 diabetes | |
| 650 | 7 | |a Fatty Acids, Nonesterified |2 NLM | |
| 650 | 7 | |a Fatty Acids |2 NLM | |
| 700 | 1 | |a Fried, Juliana Coraor |e verfasserin |4 aut | |
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| 700 | 1 | |a Sidhom, Eriene-Heidi |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Matthew R |e verfasserin |4 aut | |
| 700 | 1 | |a Marshall, Jamie L |e verfasserin |4 aut | |
| 700 | 1 | |a Arevalo, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Dvela-Levitt, Moran |e verfasserin |4 aut | |
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