Cover Story Current Issue

The prevalence of obesity and type II diabetes is growing globally at rates indicating that environment rather than genes is the principal driver. Exposures to high-fat diet and toxicants, as well as micronutrient deficiency, can impact our health and that of future generations. Only now are we beginning to identify mechanisms linking these exposures to parental and offspring health. One connection between environment and health is the epigenome. The epigenome refers to the biochemical content associated with DNA that impacts gene expression and chromatin organization. Uncovering how genomic information is organized and regulated through epigenetic processes to control gene expression and cell functions in the next generation is still in a nascent stage. 

Anne-Sophie Pepin, Christine Lafleur, Romain Lambrot, Vanessa Dumeaux, Sarah Kimmins

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Current Issue

Dietary PUFAs drive diverse system-level changes in lipid metabolism

Samuel Furse, Samuel Virtue, Stuart G. Snowden, Antonio Vidal-Puig, ... Albert Koulman

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 acideicosapentaenoic 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. Phosphatidylcholineand triglycerides showed a change in the variety more than the total number of variables, whereas phosphatidylethanolamine and phosphatidylinositolshowed 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.

Dietary PUFAs drive diverse system-level changes in lipid metabolism

Samuel Furse, Samuel Virtue, Stuart G. Snowden, Antonio Vidal-Puig, ... Albert Koulman

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 acideicosapentaenoic 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. Phosphatidylcholineand triglycerides showed a change in the variety more than the total number of variables, whereas phosphatidylethanolamine and phosphatidylinositolshowed 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.

2021 impact factor: 7.422

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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