Abstract

BackgroundThe consumption of high levels of industrial trans fatty acids (TFA) has been related to cardiovascular disease, diabetes and sudden cardiac death but the causal mechanisms are not well known. In this study, NMR and LC-MS untargeted metabolomics has been used as an approach to explore the impact of TFA intake on plasma metabolites.Methodology/Principal FindingsIn a double-blinded randomized controlled parallel-group study, 52 overweight postmenopausal women received either partially hydrogenated soybean oil, providing 15.7 g/day of TFA (trans18:1) or control oil with mainly oleic acid for 16 weeks. Subsequent to the intervention period, the subjects participated in a 12-week dietary weight loss program. Before and after the TFA intervention and after the weight loss programme, volunteers participated in an oral glucose tolerance test. PLSDA revealed elevated lipid profiles with TFA intake. NMR indicated up-regulated LDL cholesterol levels and unsaturation. LC-MS profiles demonstrated elevated levels of specific polyunsaturated (PUFA) long-chain phosphatidylcholines (PCs) and a sphingomyelin (SM) which were confirmed with a lipidomics based method. Plasma levels of these markers of TFA intake declined to their low baseline levels after the weight loss program for the TFA group and did not fluctuate for the control group. The marker levels were unaffected by OGTT.Conclusions/SignificanceThis study demonstrates that intake of TFA affects phospholipid metabolism. The preferential integration of trans18:1 into the sn-1 position of PCs, all containing PUFA in the sn-2 position, could be explained by a general up-regulation in the formation of long-chain PUFAs after TFA intake and/or by specific mobilisation of these fats into PCs. NMR supported these findings by revealing increased unsaturation of plasma lipids in the TFA group. These specific changes in membrane lipid species may be related to the mechanisms of TFA-induced disease but need further validation as risk markers.Trial registrationRegistered at clinicaltrials.gov as NCT00655902

Highlights

  • Produced trans fatty acids (TFA) are formed by partial hydrogenation of vegetable oil that changes cis configuration of double bond(s) to trans, resulting in solid fat for use in margarines and shortenings, and for commercial cooking, and manufacturing processes

  • It has been well documented that TFA intake increases lowdensity lipoprotein (LDL) cholesterol, reduces high-density lipoprotein (HDL) cholesterol, and increases the risk of cardiovascular disease [6,7]

  • All subjects in the TFA group had elevated trans18:1 residue levels at both 8 and 16 weeks of intervention, whereas the control subjects did not

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Summary

Introduction

Produced trans fatty acids (TFA) are formed by partial hydrogenation of vegetable oil that changes cis configuration of double bond(s) to trans, resulting in solid fat for use in margarines and shortenings, and for commercial cooking, and manufacturing processes. Denmark was the first country where the background level of TFA exposure was minimized because the industry after the ban in 2004 succeeded in removing these fats from more than 90% all marketed products. This is not the situation in many other countries and studies to further document and understand the causes of TFA mediated coronary heart disease (CHD) risk are still needed. The consumption of high levels of industrial trans fatty acids (TFA) has been related to cardiovascular disease, diabetes and sudden cardiac death but the causal mechanisms are not well known. NMR and LC-MS untargeted metabolomics has been used as an approach to explore the impact of TFA intake on plasma metabolites

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