Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol

J Nutr Biochem. 2019 Dec:74:108231. doi: 10.1016/j.jnutbio.2019.108231. Epub 2019 Aug 31.

Abstract

Docosahexaenoic acid (DHA) is highly concentrated in the brain, and its deficiency is associated with several neurological disorders including Alzheimer's disease. However, the currently used supplements do not appreciably enrich brain DHA, although they enrich most other tissues. We tested the hypothesis that the ability of the dietary carrier to augment brain DHA depends upon the generation of DHA-lysophosphatidylcholine (LPC), the preferred carrier of DHA across the blood brain barrier. We compared the efficacy of DHA-triacylglycerol (TAG), di-DHA phosphatidylcholine (PC) and DHA-LPC to enrich brain DHA following their gavage to normal rats for 30 days, all at a dose of 10 mg DHA/day. The results show that DHA from TAG, which is released as free DHA or monoacylglycerol during digestion and is absorbed as TAG in chylomicrons, was incorporated preferentially into adipose tissue and heart but not into brain. In contrast, LPC-DHA increased brain DHA by up to 100% but had no effect on adipose tissue. Di-DHA PC, which generates both free DHA and LPC-DHA during the digestion, enriched DHA in brain, as well as in heart and liver. Brain-derived neurotrophic factor was increased by di-DHA PC and DHA-LPC, but not by TAG-DHA, showing that enrichment of brain DHA correlated with its functional effect. We conclude that dietary DHA from TAG or from natural PC (sn-2 position) is not suitable for brain enrichment, whereas DHA from LPC (at either sn-1 or sn-2 position) or from sn-1 position of PC efficiently enriches the brain and is functionally effective.

Keywords: BDNF; Blood brain barrier; Brain omega-3 fatty acids; Intestinal barrier; Neuroinflammatory diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Arachidonic Acid / pharmacokinetics
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage*
  • Docosahexaenoic Acids / metabolism
  • Docosahexaenoic Acids / pharmacokinetics
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics
  • Lysophosphatidylcholines / administration & dosage*
  • Lysophosphatidylcholines / blood
  • Male
  • Maze Learning
  • Phosphatidylcholines / administration & dosage*
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Triglycerides / administration & dosage*

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Drug Carriers
  • Lysophosphatidylcholines
  • Phosphatidylcholines
  • Triglycerides
  • Docosahexaenoic Acids
  • Arachidonic Acid