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A lipidomic analysis approach to evaluate the response to cholesterol-lowering food intake.

ABSTRACT: Plant sterols (PS) are well known to reduce serum levels of total cholesterol and LDL-cholesterol. Lipidomics potentially provides detailed information on a wide range of individual serum lipid metabolites, which may further add to our understanding of the biological effects of PS. In this study, lipidomics analysis was applied to serum samples from a placebo-controlled, parallel human intervention study (n = 97) of 4-week consumption of two PS-enriched, yoghurt drinks differing in fat content (based on 0.1% vs. 1.5% dairy fat). A comprehensive data analysis strategy was developed and implemented to assess and compare effects of two different PS-treatments and placebo treatment. The combination of univariate and multivariate data analysis approaches allowed to show significant effects of PS intake on the serum lipidome, and helped to distinguish them from fat content and non-specific effects. The PS-enriched 0.1% dairy fat yoghurt drink had a stronger impact on the lipidome than the 1.5% dairy fat yoghurt drink, despite similar LDL-cholesterol lowering effects. The PS-enriched 0.1% dairy fat yoghurt drink reduced levels of several sphingomyelins which correlated well with the reduction in LDL-cholesterol and can be explained by co-localization of sphingomyelins and cholesterol on the surface of LDL lipoprotein. Statistically significant reductions in serum levels of two lysophosphatidylcholines (LPC(16:1), LPC(20:1)) and cholesteryl arachidonate may suggest reduced inflammation and atherogenic potential. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-011-0384-2) contains supplementary material, which is available to authorized users.

SUBMITTER: Szymanska E

PROVIDER: S-EPMC3465648 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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A lipidomic analysis approach to evaluate the response to cholesterol-lowering food intake.

Szymańska Ewa E van Dorsten Ferdinand A FA Troost Jorne J Paliukhovich Iryna I van Velzen Ewoud J J EJ Hendriks Margriet M W B MM Trautwein Elke A EA van Duynhoven John P M JP Vreeken Rob J RJ Smilde Age K AK

Metabolomics : Official journal of the Metabolomic Society 20111207 5

Plant sterols (PS) are well known to reduce serum levels of total cholesterol and LDL-cholesterol. Lipidomics potentially provides detailed information on a wide range of individual serum lipid metabolites, which may further add to our understanding of the biological effects of PS. In this study, lipidomics analysis was applied to serum samples from a placebo-controlled, parallel human intervention study (n = 97) of 4-week consumption of two PS-enriched, yoghurt drinks differing in fat content ( ...[more]

PMID: 23060736

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Project description:ImportanceObservational studies suggest that statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, may be associated with beneficial effects in many noncardiovascular diseases.ObjectiveTo construct a weighted HMG-CoA reductase (HMGCR) gene genetic risk score (GRS) using variants in the HMGCR gene affecting low-density lipoprotein cholesterol as an instrumental variable for mendelian randomization analyses to test associations with candidate noncardiovascular phenotypes previously associated with statin use in observational studies.Design, setting, and participantsThis cohort study included 53 385 unrelated adults of European ancestry with genome-wide genotypes available from BioVU (a practice-based biobank, used for discovery) and 30 444 unrelated adults with European ancestry available in the Electronic Medical Records and Genomics (eMERGE; a research consortium that conducts genetic research using electronic medical records, used for replication). The study was conducted from February 6, 2015, through April 31, 2019; data analysis was performed from August 26, 2019, through December 22, 2020.InterventionsAn HMGCR GRS was calculated.Main outcomes and measuresThe association between the HMGCR GRS and the presence or absence of 22 noncardiovascular phenotypes previously associated with statin use in clinical studies.ResultsOf the 53 385 individuals in BioVU, 29 958 (56.1%) were women; mean (SD) age was 59.9 (15.6) years. The finding between the HMGCR GRS and the noncardiovascular phenotypes of interest in this cohort was significant only for type 2 diabetes. An HMGCR GRS equivalent to a 10-mg/dL decrease in the low-density lipoprotein cholesterol level was associated with an increased risk of type 2 diabetes (odds ratio [OR], 1.09; 95% CI, 1.04-1.15; P = 5.58 × 10-4). The HMGCR GRS was not associated with other phenotypes; the closest were increased risk of Parkinson disease (OR, 1.30; 95% CI, 1.07-1.58; P = .007) and kidney failure (OR, 1.18; 95% CI, 1.05-1.34; P = .008). Of the 30 444 individuals in eMERGE, 16 736 (55.0%) were women; mean (SD) age was 68.7 (15.4) years. The association between the HMGCR GRS and type 2 diabetes was replicated in this cohort (OR, 1.09; 95% CI, 1.01-1.17; P = .02); however, the HMGCR GRS was not associated with Parkinson disease (OR, 0.93; 95% CI, 0.75-1.16; P = .53) and kidney failure (OR, 1.18; 95% CI, 0.98-1.41; P = .08) in the eMERGE cohort.Conclusions and relevanceA mendelian randomization approach using variants in the HMGCR gene replicated the association between statin use and increased type 2 diabetes risk but provided no strong evidence for pleiotropic effects of statin-induced decrease of the low-density lipoprotein cholesterol level on other diseases.

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A lipidomic analysis approach to evaluate the response to cholesterol-lowering food intake.

Publications

A lipidomic analysis approach to evaluate the response to cholesterol-lowering food intake.

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