Effects of changing from a diet with saturated fat to a diet with n-6 polyunsaturated fat on the serum metabolome in relation to cardiovascular disease risk factors

Kristina Pigsborg, Gözde Gürdeniz, Oscar Daniel Rangel-Huerta, Kirsten B Holven, Lars Ove Dragsted, Stine M Ulven, Kristina Pigsborg, Gözde Gürdeniz, Oscar Daniel Rangel-Huerta, Kirsten B Holven, Lars Ove Dragsted, Stine M Ulven

Abstract

Purpose: Replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers.

Methods: In an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25-70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups.

Results: PLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia.

Conclusion: The serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT01679496 on September 6th 2012.

Keywords: Cardiovascular risk markers; Fatty acids; Metabolomics; Nordic diet; Phospholipids.

Conflict of interest statement

Dr. Ulven and Dr. Holven received research grants from Mills DA to partially fund the study. None owns any stocks or serves as an advisory board in the company. The authors declare they have no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
PC1 vs. PC2 biplot based on features from the final PLS-DA model (AUC = 0.83, classification error = 0.23) for diet group separations. Subjects are coloured according to diet (red diamonds for Ex-diet and green squares for C-diet) and identified metabolites for the diets are highlighted (grey points), PC(P) phosphatidylcholine plasmalogen, PC phosphatidylcholine, RT retention time
Fig. 2
Fig. 2
Hierarchical clustering analysis of the serum metabolites differentiating the Ex-diet diet group from the C-diet group diet based on Spearman correlation coefficients; only significant correlations (p < 0.05) are depicted. Unk unknown, PC(P) phosphatidylcholine plasmalogen, PC phosphatidylcholine, m/z mass to charge ratio, RT retention time

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Source: PubMed

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