Effect of trans Fatty Acid Intake on LC-MS and NMR Plasma Profiles

G├╝rdeniz G; Rago D; Bendsen NT; Savorani F; Astrup A; Dragsted LO
Journal
PLoS One
Paper attributed to Project(s)

Introduction
Industrially 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. Partially hardened oils are appealing for food industry owing to their properties such as long shelf life, their stability during deep-frying and their semi-solidity. However, consumption of TFA in the human diet has been associated with an increased risk of developing cardiovascular disease [1], [2], diabetes [3], and sudden death from cardiac causes [4]. TFA has now been banned in a few countries, including Austria, Denmark, Hungary, Sweden, and Switzerland as well as in California and in the New York municipality in the USA. 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. However, 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 therefore still needed. This risk has been linked to the impact of TFA on lipoprotein metabolism, inflammation, and endothelial function [5]. It has been well documented that TFA intake increases low-density lipoprotein (LDL) cholesterol, reduces high-density lipoprotein (HDL) cholesterol, and increases the risk of cardiovascular disease [6], [7]. Nevertheless, the incidence of CHD reported in prospective studies as a result of TFA exposure has been greater than that predicted by increased serum lipids or inflammation alone. Thus, the observed associations between TFA consumption and cardiovascular disease events cannot be explained only by changes in lipoprotein levels, triglycerides, apolipoprotein (Apo) B/ApoAI ratio and C-reactive protein [8], implying that the mechanisms behind the adverse effects of TFAs are not fully understood. TFA exposure has also been associated with a higher risk of fatal ischemic heart disease [9] and sudden cardiac death [10]. Although the potential mechanism between TFA and sudden cardiac death is unclear, some have suggested that TFA may modulate cardiac membrane ion channel function [11] or have proarrhythmic properties, affecting cardiovascular electrophysiology [2].

Some evidence also pointed to a possible effect of TFA on obesity. A dietary 16-week intervention study was conducted here in 2008 by Bendsen et al. [13] to examine the effect of a high intake of industrially produced TFA (trans18:1) compared to the cis analog (cis18:1) on central obesity and insulin sensitivity. The low TFA background in Denmark made it feasible to conduct a TFA intervention against a clean background in the control group to unambiguously assess any shorter-term effects on central fat deposition or other risk markers of CHD. However, the study did not provide evidence for effects on obesity development. In order to search for new hypotheses and fill the gap between TFA intake and its detrimental health impacts, we selected an untargeted metabolomics approach to profile plasma samples from this study.

Metabolic profiling allows semiquantification of hundreds of metabolites in blood samples and might provide a unique insight into the potential underlying mechanisms. Many studies have demonstrated metabolomics as a powerful tool to understand responses of individuals with respect to their gene expression or alterations in their lifestyles and diets [12]. The application of liquid chromatography mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) in metabolomics for measurement of a wide range of metabolites in various biofluids has been well established. NMR provides high reproducibility and is a powerful tool in terms of quantification, whereas LC-MS is more sensitive, allowing detection of a larger number of chemical compounds, albeit with lower reproducibility.

Our results from the untargeted metabolomics analysis of the TFA intervention study revealed an increased presence during TFA intake of membrane-derived, specific long chain polyunsaturated fatty acid (PUFA)-containing PCs and a SM, suggesting the possibility of using these compounds as individual markers of TFA integration into plasma membranes

DANORC is supported by the
The Danish Council for Strategic Research
Institute of Preventive Medicine
Frederiksberg Hospital
Nordre Fasanvej 57
2000 Frederiksberg
Denmark
Tel.: +45 38163025