Unbound free fatty acid profiles in human plasma and the unexpected absence of unbound palmitoleate
Open accessAbstract
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.
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Under physiological conditions, FFAs circulate in the blood primarily in an albumin-bound state, but only the unbound fraction is biologically active and amounts to just 1.6 nM, which is less than 10−5 of total FFAs.
“Under physiological conditions, FFAs circulate in the blood primarily in an albumin-bound state [138,141,142]. However, only the unbound fraction is biologically active and amounts to just 1.6 nM, which is less than 10−5 of total FFAs [141].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [141]
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- Authors
- Huber, A. H., & Kleinfeld, A. M.
- Corresponding author
- Kleinfeld, Alan M.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 58
- Issue
- 3
- Pages
- 578-585
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC5335587
- OpenAlex
- W2572908265
- Cited by
- 53
- References
- 29
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 5 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 4
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Standards and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- myristic acid, long-chain fatty acids, fatty acid binding protein, human plasma
- MeSH terms
- Fatty Acids, Monounsaturated, Fatty Acids, Nonesterified, Fluorescence, Humans, 2-Naphthylamine, Myristic Acid, Lipid Metabolism, Fatty Acid-Binding Proteins, Healthy Volunteers
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