Development and validation of a robust automated analysis of plasma phospholipid fatty acids for metabolic phenotyping of large epidemiological studies

Wang, Laura Y.; Summerhill, Keith; Rodriguez-Canas, Carmen; Mather, Ian H.; Patel, Pinal; Eiden, Michael; Young, Stephen P.; Forouhi, Nita G.; Koulman, Albert

doi:10.1186/gm443

Cited by 39 publications

(49 citation statements)

References 21 publications

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“…20 : 4 n -6 + 20 : 3 n -3 co-eluted, but as 20 : 3 n -3 concentration in human samples is negligible, this peak was identified as 20 : 4 n -6 [43] a Values are given as means ± SEM b Overall effect of treatment based on change-from-baseline was calculated by mixed model analysis, with adjustments made for fixed effects of baseline values of the assessed variable, period, treatment, age, gender and BMI. Participant was included as a random effect…”

Section: Resultsmentioning

confidence: 99%

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial

Markey

Vasilopoulou

Kliem

et al. 2017

Nutr J

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BackgroundDairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status.MethodsIn a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA).ResultsFollowing the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet.ConclusionThe food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance.Trial registrationClinicalTrials.gov Identifier: NCT02089035, date 05-01-2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-017-0249-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial

Markey

Vasilopoulou

Kliem

et al. 2017

Nutr J

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“…Fatty acids were profiled at the Medical Research Council Human Nutrition Research (Cambridge, UK); profiling involved analysis of plasma samples stored at baseline at −196°C (or −150°C in Denmark)—a temperature at which fatty acids remain stable. 6 The assay methods have previously been described 23 and included hydrolysis and methylation to convert phospholipid fatty acids into more volatile fatty acid methyl esters and separation of the different fatty acids by gas chromatography (J&W HP-88, 30 m length, 0·25 mm internal diameter [Agilent Technologies, CA, USA]) equipped with flame ionisation detection (7890N GC [Agilent Technologies]). Samples from people with type 2 diabetes and subcohort participants were processed in random order by centre, and laboratory staff were masked to all participant characteristics by the use of anonymised aliquots.…”

Section: Methodsmentioning

confidence: 99%

“…We used human and equine plasma (Sera Laboratories International, West Sussex, UK) for quality control. 23 …”

Section: Methodsmentioning

confidence: 99%

Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study

Forouhi

Koulman

Sharp

et al. 2014

The Lancet Diabetes & Endocrinology

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SummaryBackgroundConflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants.MethodsThe EPIC-InterAct case-cohort study includes 12 403 people with incident type 2 diabetes and a representative subcohort of 16 154 individuals who were selected from a cohort of 340 234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis.FindingsSFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09–1·22], palmitic acid 1·26 [1·15–1·37], and stearic acid 1·06 [1·00–1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73–0·85] for pentadecanoic acid and 0·67 [0·63–0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses.InterpretationDifferent individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed.FundingEU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative.

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“…Subfractionation of adipose tissue was performed as reported (33). Shotgun lipidomics were performed as described previously (26,34).…”

Section: Methodsmentioning

confidence: 99%

Adaptive Changes of the Insig1/SREBP1/SCD1 Set Point Help Adipose Tissue to Cope With Increased Storage Demands of Obesity

et al. 2013

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The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.

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Development and validation of a robust automated analysis of plasma phospholipid fatty acids for metabolic phenotyping of large epidemiological studies

Cited by 39 publications

References 21 publications

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial

Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study

Adaptive Changes of the Insig1/SREBP1/SCD1 Set Point Help Adipose Tissue to Cope With Increased Storage Demands of Obesity

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