Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid

  title={Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid},
  author={Long N. Nguyen and Dongliang Ma and Guanghou Shui and Peiyan Wong and Amaury Cazenave-Gassiot and Xiaodong Zhang and Markus R. Wenk and Eyleen L. K. Goh and David L. Silver},
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood–brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily… 

The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain

It is demonstrated that Mfsd2a is uniquely required postnatally at the blood-brain barrier for normal brain growth and DHA accretion, with DHA deficiency preceding the onset of microcephaly.

Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid

The findings identify AceDoPC as an efficient way to specifically target DHA to the brain, which would allow potential preventive and therapeutic approaches for neurological diseases.

Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development*

It is demonstrated that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of MfsD2a expression in the eye.

Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome

The results establish a link between transport of DHA and LPCs by MFSD2A and human brain growth and function, presenting the first evidence of monogenic disease related to transport ofDHA in humans.

Dietary docosahexaenoic acid supplementation enhances expression of fatty acid‐binding protein 5 at the blood–brain barrier and brain docosahexaenoic acid levels

It is demonstrated that DHA can increase BBB expression of FABP5, as well as fatty acid transporters, overall increasing brain DHA levels.

Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain

It is discovered that a member of the long-chain acyl-CoA synthetase family, Acsl6, is required for the enrichment of DHA in the brain by generating an AcSl6-deficient mouse (Acsl6−/−).

Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye.

Beyond its role in brain development, LPC-DHA uptake in the brain and eye negatively regulates de novo lipogenesis and the proposed transport mechanism of Mfsd2a is focused on.

Specific uptake of DHA by the brain from a structured phospholipid, AceDoPC®

Findings suggested that DHA is better incorporated into the brain when esterified at the sn- 2 position of a lysophosphatidylcholine (LysoPC-DHA).

Fatty Acid-Binding Protein 5 Facilitates the Blood-Brain Barrier Transport of Docosahexaenoic Acid.

It is demonstrated that FABP5 binds to DHA and is involved in the brain endothelial cell uptake and subsequent BBB transport of DHA, confirming the importance of this cytoplasmic carrier protein in the CNS exposure of this PUFA essential for neuronal function.



Novel Metabolism of Docosahexaenoic Acid in Neural Cells*

In this review, biochemical mechanisms for enriching and metabolizing DHA in neural cells are discussed in the context of their biological significance in neuronal function.

Health benefits of docosahexaenoic acid (DHA)

The association of DHA deficiency with depression is the reason for the robust positive correlation between depression and myocardial infarction, and patients with cardiovascular disease or Type II diabetes are often advised to adopt a low-fat diet with a high proportion of carbohydrate.

Major Facilitator Superfamily Domain-Containing Protein 2a (MFSD2A) Has Roles in Body Growth, Motor Function, and Lipid Metabolism

Results indicate that Mfsd2a is a nutritionally regulated gene that plays myriad roles in body growth and development, motor function, and lipid metabolism, and suggest that the ligand(s) that are transported by MFSD2A play important roles in these physiological processes and await future identification.

Dietary (n-3) fatty acids and brain development.

  • S. Innis
  • Psychology, Medicine
    The Journal of nutrition
  • 2007
A better understanding of development and age-specific changes in DHA transfer and function in the developing brain may provide important insight into the role of DHA in developmental disorders in infants and children, as well as at other stages of the lifespan.

Mechanisms of action of docosahexaenoic acid in the nervous system

Through its effects on PS, DHA may play an important role in the regulation of cell signaling and in cell proliferation, and progress has been made recently in nuclear magnetic responance studies to delineate differences in molecular structure and order in biomembranes due to subtle changes in the degree of phospholipid unsaturation.

Characterization of plasma unsaturated lysophosphatidylcholines in human and rat.

Substantial concentrations of 2-acyl-lysoPtdCho are present in plasma and are available for tissue uptake, where they can be reacylated at the sn-1 position to form membrane phospholipids.

Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions

It is found that lifelong n-3 PUFAs dietary insufficiency specifically ablates long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens, and identifies a plausible synaptic substrate for the behavioral alterations caused by the n- 3 PUfAs deficiency that is often observed in western diets.

Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.

  • P. Kidd
  • Psychology
    Alternative medicine review : a journal of clinical therapeutic
  • 2007
Meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder, and omega-3 phospholipid supplements that combine DHA/EPA andospholipids into the same molecule have shown marked promise in early clinical trials.

Phospholipid supplementation reverses behavioral and biochemical alterations induced by n-3 polyunsaturated fatty acid deficiency in mice.

Egg yolk or cerebral phospholipids are an effective source of n-3 PUFA for reversing behavioral changes and altered fatty acid composition induced by a diet deficient in n-2 polyunsaturated fatty acids (PUFA).

The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases

A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.