Dietary PUFAs drive diverse system-level changes in lipid metabolism.
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Authors
Furse, Samuel
Virtue, Samuel
Snowden, Stuart G
Vidal-Puig, Antonio
Stevenson, Philip C
Chiarugi, Davide
Publication Date
2022-05Journal Title
Mol Metab
ISSN
2212-8778
Publisher
Elsevier BV
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Furse, S., Virtue, S., Snowden, S. G., Vidal-Puig, A., Stevenson, P. C., Chiarugi, D., & Koulman, A. (2022). Dietary PUFAs drive diverse system-level changes in lipid metabolism.. Mol Metab https://doi.org/10.1016/j.molmet.2022.101457
Abstract
OBJECTIVE: Polyunsaturated fatty acid (PUFA) supplements have been trialled as a treatment for a number of conditions and produced a variety of results. This variety is ascribed to the supplements, that often comprise a mixture of fatty acids, and to different effects in different organs. In this study, we tested the hypothesis that the supplementation of individual PUFAs has system-level effects that are dependent on the molecular structure of the PUFA. METHODS: We undertook a network analysis using Lipid Traffic Analysis to identify both local and system-level changes in lipid metabolism using publicly available lipidomics data from a mouse model of supplementation with FA(20:4n-6), FA(20:5n-3), and FA(22:6n-3); arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, respectively. Lipid Traffic Analysis is a new computational/bioinformatics tool that uses the spatial distribution of lipids to pinpoint changes or differences in control of metabolism, thereby suggesting mechanistic reasons for differences in observed lipid metabolism. RESULTS: There was strong evidence for changes to lipid metabolism driven by and dependent on the structure of the supplemented PUFA. Phosphatidylcholine and triglycerides showed a change in the variety more than the total number of variables, whereas phosphatidylethanolamine and phosphatidylinositol showed considerable change in both which variables and the number of them, in a highly PUFA-dependent manner. There was also evidence for changes to the endogenous biosynthesis of fatty acids and to both the elongation and desaturation of fatty acids. CONCLUSIONS: These results show that the full biological impact of PUFA supplementation is far wider than any single-organ effect and implies that supplementation and dosing with PUFAs require a system-level assessment.
Sponsorship
BBSRC (BB/M027252/1)
Funder references
Biotechnology and Biological Sciences Research Council (BB/M027252/2)
Biotechnology and Biological Sciences Research Council (BB/M027252/1)
Medical Research Council (MC_UU_12012/2)
British Heart Foundation (RG/18/7/33636)
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (G0802051)
Medical Research Council (MC_G0802535)
Medical Research Council (G0400192)
MRC (MC_UU_00014/2)
Biotechnology and Biological Sciences Research Council (BB/P028195/1)
Identifiers
External DOI: https://doi.org/10.1016/j.molmet.2022.101457
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336578
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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