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Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain.

ABSTRACT: Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.

SUBMITTER: Chen CT

PROVIDER: S-EPMC4625162 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain.

Chen Chuck T CT Kitson Alex P AP Hopperton Kathryn E KE Domenichiello Anthony F AF Trépanier Marc-Olivier MO Lin Lauren E LE Ermini Leonardo L Post Martin M Thies Frank F Bazinet Richard P RP

Scientific reports 20151029

Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. ...[more]

PMID: 26511533

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Project description:Study questionAre non-esterified fatty acid (NEFA) kinetics altered in women with polycystic ovary syndrome (PCOS)?Summary answerWomen with PCOS, particularly obese subjects, have dysregulated plasma NEFA kinetics in response to changes in plasma insulin and glucose levels, which are associated with insulin resistance (IR) independently of the fasting plasma NEFA levels.What is known alreadyElevated plasma NEFA levels are associated with IR in many disorders, although the homeostasis of NEFA kinetics and its relationship to IR in women with PCOS is unknown.Study design, size, durationWe prospectively compared insulin sensitivity and NEFA kinetics in 29 PCOS and 29 healthy controls women matched for BMI.Participants/materials, setting, methodsThis study was conducted in a tertiary institution. Plasma NEFA, glucose and insulin levels were assessed during a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT). Minimal models were used to assess insulin sensitivity (Si) and NEFA kinetics (i.e. model-derived initial plasma NEFA level [NEFA0], phi constant [Φ], reflecting glucose-mediated inhibition of lipolysis and measures of maximum rate of lipolysis [SFFA] and NEFA uptake from plasma [KFFA]).Main results and the role of chanceThe study provides new evidence that women with PCOS have defective NEFA kinetics characterized by: (i) lower basal plasma NEFA levels, measured directly and modeled (NEFA0), and (ii) a greater glucose-mediated inhibition of lipolysis in the remote or interstitial space (reflected by a lower affinity constant [Φ]). There were no differences, however, in the maximal rates of adipose tissue lipolysis (SFFA) and the rate at which NEFA leaves the plasma pool (KFFA). The differences observed in NEFA kinetics were exacerbated, and almost exclusively observed, in the obese PCOS subjects.Limitations, reasons for cautionOur study did not study NEFA subtypes. It was also cross-sectional and based on women affected by PCOS as defined by the 1990 National Institutes of Health (NIH) criteria (i.e. Phenotypes A and B) and identified in the clinical setting. Consequently, extrapolation of the present data to other phenotypes of PCOS should be made with caution. Furthermore, our data is exploratory and therefore requires validation with a larger sample size.Wider implications of the findingsDysfunction in NEFA kinetics may be a marker of metabolic dysfunction in nondiabetic obese women with PCOS and may be more important than simply assessing circulating NEFA levels at a single point in time for understanding the mechanism(s) underlying the IR of PCOS.Study funding/competing interest(s)This work was supported by NIH grants R01-DK073632 and R01-HD29364 to R.A.; a Career Development Award from MD Medical Group, Moscow, RF, to D.L. and Augusta University funds to Y.-H.C. RA serves as consultant to Ansh Labs, Medtronics, Spruce Biosciences and Latitude Capital. U.E., Z.A., D.L., R.M., Y.-H.C., R.C.B. and Y.D.I.C. have no competing interests to declare.Trial registration numberNot applicable.

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Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain.

Publications

Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain.

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