A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.

A balanced omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio has been linked to health benefits and the prevention of many chronic diseases. Current dietary intervention studies with different sources of omega-3 fatty acids (omega-3) lack appropriate control diets and carry many other confound...

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Main Authors: Giuseppe Astarita, Jennifer H McKenzie, Bin Wang, Katrin Strassburg, Angela Doneanu, Jay Johnson, Andrew Baker, Thomas Hankemeier, James Murphy, Rob J Vreeken, James Langridge, Jing X Kang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3997567?pdf=render
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author Giuseppe Astarita
Jennifer H McKenzie
Bin Wang
Katrin Strassburg
Angela Doneanu
Jay Johnson
Andrew Baker
Thomas Hankemeier
James Murphy
Rob J Vreeken
James Langridge
Jing X Kang
author_facet Giuseppe Astarita
Jennifer H McKenzie
Bin Wang
Katrin Strassburg
Angela Doneanu
Jay Johnson
Andrew Baker
Thomas Hankemeier
James Murphy
Rob J Vreeken
James Langridge
Jing X Kang
author_sort Giuseppe Astarita
collection DOAJ
description A balanced omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio has been linked to health benefits and the prevention of many chronic diseases. Current dietary intervention studies with different sources of omega-3 fatty acids (omega-3) lack appropriate control diets and carry many other confounding factors derived from genetic and environmental variability. In our study, we used the fat-1 transgenic mouse model as a proxy for long-term omega-3 supplementation to determine, in a well-controlled manner, the molecular phenotype associated with a balanced omega-6/omega-3 ratio. The fat-1 mouse can convert omega-6 to omega-3 PUFAs, which protect against a wide variety of diseases including chronic inflammatory diseases and cancer. Both wild-type (WT) and fat-1 mice were subjected to an identical diet containing 10% corn oil, which has a high omega-6 content similar to that of the Western diet, for a six-month duration. We used a multi-platform lipidomic approach to compare the plasma lipidome between fat-1 and WT mice. In fat-1 mice, an unbiased profiling showed a significant increase in the levels of unesterified eicosapentaenoic acid (EPA), EPA-containing cholesteryl ester, and omega-3 lysophosphospholipids. The increase in omega-3 lipids is accompanied by a significant reduction in omega-6 unesterified docosapentaenoic acid (omega-6 DPA) and DPA-containing cholesteryl ester as well as omega-6 phospholipids and triacylglycerides. Targeted lipidomics profiling highlighted a remarkable increase in EPA-derived diols and epoxides formed via the cytochrome P450 (CYP450) pathway in the plasma of fat-1 mice compared with WT mice. Integration of the results of untargeted and targeted analyses has identified a lipidomic biosignature that may underlie the healthful phenotype associated with a balanced omega-6/omega-3 ratio, and can potentially be used as a circulating biomarker for monitoring the health status and the efficacy of omega-3 intervention in humans.
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spelling doaj.art-9816b672132b4ef1a7ee788d320221212022-12-21T19:18:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9622110.1371/journal.pone.0096221A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.Giuseppe AstaritaJennifer H McKenzieBin WangKatrin StrassburgAngela DoneanuJay JohnsonAndrew BakerThomas HankemeierJames MurphyRob J VreekenJames LangridgeJing X KangA balanced omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio has been linked to health benefits and the prevention of many chronic diseases. Current dietary intervention studies with different sources of omega-3 fatty acids (omega-3) lack appropriate control diets and carry many other confounding factors derived from genetic and environmental variability. In our study, we used the fat-1 transgenic mouse model as a proxy for long-term omega-3 supplementation to determine, in a well-controlled manner, the molecular phenotype associated with a balanced omega-6/omega-3 ratio. The fat-1 mouse can convert omega-6 to omega-3 PUFAs, which protect against a wide variety of diseases including chronic inflammatory diseases and cancer. Both wild-type (WT) and fat-1 mice were subjected to an identical diet containing 10% corn oil, which has a high omega-6 content similar to that of the Western diet, for a six-month duration. We used a multi-platform lipidomic approach to compare the plasma lipidome between fat-1 and WT mice. In fat-1 mice, an unbiased profiling showed a significant increase in the levels of unesterified eicosapentaenoic acid (EPA), EPA-containing cholesteryl ester, and omega-3 lysophosphospholipids. The increase in omega-3 lipids is accompanied by a significant reduction in omega-6 unesterified docosapentaenoic acid (omega-6 DPA) and DPA-containing cholesteryl ester as well as omega-6 phospholipids and triacylglycerides. Targeted lipidomics profiling highlighted a remarkable increase in EPA-derived diols and epoxides formed via the cytochrome P450 (CYP450) pathway in the plasma of fat-1 mice compared with WT mice. Integration of the results of untargeted and targeted analyses has identified a lipidomic biosignature that may underlie the healthful phenotype associated with a balanced omega-6/omega-3 ratio, and can potentially be used as a circulating biomarker for monitoring the health status and the efficacy of omega-3 intervention in humans.http://europepmc.org/articles/PMC3997567?pdf=render
spellingShingle Giuseppe Astarita
Jennifer H McKenzie
Bin Wang
Katrin Strassburg
Angela Doneanu
Jay Johnson
Andrew Baker
Thomas Hankemeier
James Murphy
Rob J Vreeken
James Langridge
Jing X Kang
A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.
PLoS ONE
title A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.
title_full A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.
title_fullStr A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.
title_full_unstemmed A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.
title_short A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.
title_sort protective lipidomic biosignature associated with a balanced omega 6 omega 3 ratio in fat 1 transgenic mice
url http://europepmc.org/articles/PMC3997567?pdf=render
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