Dietary PUFAs drive diverse system-level changes in lipid metabolism

Mol Metab. 2022 May;59:101457. doi: 10.1016/j.molmet.2022.101457. Epub 2022 Feb 9.


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.

Keywords: Lipid metabolism; Metabolic network; PUFA supplementation; Traffic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Docosahexaenoic Acids / metabolism
  • Eicosapentaenoic Acid / metabolism
  • Fatty Acids
  • Fatty Acids, Unsaturated* / metabolism
  • Lipid Metabolism*
  • Mice


  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid