Dataset Information

Unbound free fatty acid profiles in human plasma and the unexpected absence of unbound palmitoleate.

ABSTRACT: We determined for the first time the profiles of the nine most abundant unbound FFAs (FFAus) in human plasma. Profiles were determined for a standard reference plasma of pooled healthy adults for which the Lipid MAPSMAPS Consortium had determined the total FFA profiles. Measurements were performed by using 20 different acrylodan-labeled fatty acid binding protein mutants (probes), which have complementary specificities for the nine FFAs that comprise more than 96% of long-chain plasma FFA. The acrylodan fluorescence emission for each probe changes upon binding a FFAu. The plasma concentrations of each of the nine FFAus were determined by combining the measured fluorescence ratios of the 20 probes. The total molar FFAu concentration accounted for <10^-5 of the total FFA concentration, and the mole fractions of the FFAu profiles were substantially different than the total FFA profiles. Myristic acid, for example, comprises 22% of the unbound versus 2.8% of the total. The most surprising difference is our finding of zero unbound cis-9-palmitoleic acid (POA), whereas the total POA was 7.2%. An unidentified plasma component appears to specifically prevent the release of POA. FFAus are the physiologically active FFAs, and plasma FFAu profiles may provide novel information about human health.

SUBMITTER: Huber AH

PROVIDER: S-EPMC5335587 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Unbound free fatty acid profiles in human plasma and the unexpected absence of unbound palmitoleate.

Huber Andrew H AH Kleinfeld Alan M AM

Journal of lipid research 20170112 3

We determined for the first time the profiles of the nine most abundant unbound FFAs (FFAus) in human plasma. Profiles were determined for a standard reference plasma of pooled healthy adults for which the Lipid MAPSMAPS Consortium had determined the total FFA profiles. Measurements were performed by using 20 different acrylodan-labeled fatty acid binding protein mutants (probes), which have complementary specificities for the nine FFAs that comprise more than 96% of long-chain plasma FFA. The a ...[more]

PMID: 28082409

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Project description:Background: Unbound free fatty acids (FFAu) are the bioactive fraction of plasma free fatty acids (FFA). Most plasma FFA are bound to albumin. Only when FFA dissociate from albumin, do they become biologically active.Objective: To measure the first FFAu profiles in human infants and to measure these profiles before and during intravenous administration of the soybean lipid, intralipid (IL).Study design: The study population was 16 premature infants, from a parent study of 130 infants with birth weights 500-2000 g and gestational age 23-34 weeks. The infants chosen had plasma samples of ≥120 µL (volume needed for each FFAu profile measurement) in the first day of life. Infants received IL infusions starting in the second day of life at 1 g/kg/day, increasing by 1-g/kg/day daily up to 3 g/kg/day. FFAu profiles were determined during IL infusion when plasma was available. Profiles are the concentrations of the nine most abundant long-chain FFAu and were determined using novel fluorescent probes.Results: Before intralipid infusion unbound myristic acid was the dominant FFAu, as high as 78% of the total FFAu (sum of the 9 FFAu). In contrast, unbound linoleic acid was 0% in all infants. With increasing infusion of IL to 3 g/kg/day, unbound linoleic increased to 26% of the total FFAu, with unbound oleic, myristic, and linolenic acid the second, third and fourth most abundant. The average total FFAu concentration also increased from 4 nM before intralipid to 53 nM at 3 g/kg/day. During IL infusion the FFAu profiles approached the fatty acid composition of intralipid at 3 g/kg/day.Conclusions: This first study of FFAu profiles in neonates revealed that before IL infusion unbound linoleic acid was zero in all 16 infants and levels of myristic acid were exceptionally large, as much as 78% of the total FFAu profile. These results suggest important and previously unrecognized roles of lipid metabolism in early development. Zero unbound linoleic acid before IL infusion may help promote closure of the ductus arteriosus but after IL infusion, synthesis of arachidonic from linoleic acid may tend to promote patency. The high levels of unbound myristate may be needed for immediate neonatal energy needs.

Project description: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. 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.In 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.This 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.Registered at clinicaltrials.gov as NCT00655902.

Dataset Information

Unbound free fatty acid profiles in human plasma and the unexpected absence of unbound palmitoleate.

Publications

Unbound free fatty acid profiles in human plasma and the unexpected absence of unbound palmitoleate.

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