Dietary PUFAs drive diverse system-level changes in lipid metabolism
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 st...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877822000266 |
| _version_ | 1818017893555634176 |
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| author | Samuel Furse Samuel Virtue Stuart G. Snowden Antonio Vidal-Puig Philip C. Stevenson Davide Chiarugi Albert Koulman |
| author_facet | Samuel Furse Samuel Virtue Stuart G. Snowden Antonio Vidal-Puig Philip C. Stevenson Davide Chiarugi Albert Koulman |
| author_sort | Samuel Furse |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:32:35Z |
| format | Article |
| id | doaj.art-07370932cfd04abbb2b26d8fc678dc0e |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-14T07:32:35Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-07370932cfd04abbb2b26d8fc678dc0e2022-12-22T02:05:48ZengElsevierMolecular Metabolism2212-87782022-05-0159101457Dietary PUFAs drive diverse system-level changes in lipid metabolismSamuel Furse0Samuel Virtue1Stuart G. Snowden2Antonio Vidal-Puig3Philip C. Stevenson4Davide Chiarugi5Albert Koulman6Core Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK; Royal Botanic Gardens, Kew, Kew Green, Richmond, Surrey, TW9 3AE, UK; Corresponding author. Core Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK.Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UKBiology Department, Royal Holloway College, University of London, UK; Centro de Investigacion Principe Felipe, 46012 Valencia, SpainWellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UKRoyal Botanic Gardens, Kew, Kew Green, Richmond, Surrey, TW9 3AE, UK; Natural Resources Institute, University of Greenwich, Chatham, Kent ME4 4TB, UKBioinformatics and Biostatistics Core, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UKCore Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK; Corresponding author. Core Metabolomics and Lipidomics Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Treatment Centre, Keith Day Road Cambridge, CB2 0QQ, UK.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.http://www.sciencedirect.com/science/article/pii/S2212877822000266Lipid metabolismPUFA supplementationTraffic analysisMetabolic network |
| spellingShingle | Samuel Furse Samuel Virtue Stuart G. Snowden Antonio Vidal-Puig Philip C. Stevenson Davide Chiarugi Albert Koulman Dietary PUFAs drive diverse system-level changes in lipid metabolism Molecular Metabolism Lipid metabolism PUFA supplementation Traffic analysis Metabolic network |
| title | Dietary PUFAs drive diverse system-level changes in lipid metabolism |
| title_full | Dietary PUFAs drive diverse system-level changes in lipid metabolism |
| title_fullStr | Dietary PUFAs drive diverse system-level changes in lipid metabolism |
| title_full_unstemmed | Dietary PUFAs drive diverse system-level changes in lipid metabolism |
| title_short | Dietary PUFAs drive diverse system-level changes in lipid metabolism |
| title_sort | dietary pufas drive diverse system level changes in lipid metabolism |
| topic | Lipid metabolism PUFA supplementation Traffic analysis Metabolic network |
| url | http://www.sciencedirect.com/science/article/pii/S2212877822000266 |
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