The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain

@article{Chan2018TheLT,
  title={The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain},
  author={Jia Pei Chan and Bernice H. Wong and Cheen Fei Chin and Dwight Lark Anolin Galam and Juat Chin Foo and Loo Chin Wong and Sujoy Ghosh and Markus R. Wenk and Amaury Cazenave-Gassiot and David L. Silver},
  journal={PLoS Biology},
  year={2018},
  volume={16}
}
Brain development requires a massive increase in brain lipogenesis and accretion of the essential omega-3 fatty acid docosahexaenoic acid (DHA). Brain acquisition of DHA is primarily mediated by the transporter Major Facilitator Superfamily Domain containing 2a (Mfsd2a) expressed in the endothelium of the blood-brain barrier (BBB) and other abundant cell types within the brain. Mfsd2a transports DHA and other polyunsaturated fatty acids (PUFAs) esterified to lysophosphatidylcholine (LPC-DHA… 
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Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye.
TLDR
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.
Acyl-CoA synthetase 6 is required for brain docosahexaenoic acid retention and neuroprotection during aging
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It is discovered that loss of long-chain acyl-CoA synthetase 6 in mice (Acsl6–/–) depletes brain membrane phospholipid DHA levels, independent of diet, and suggested that ACSL6 promotes membrane DHA enrichment in neurons, but not in astrocytes, and is important for neuronal DHA Levels across the life span.
Omega-3 Docosahexaenoic Acid Is a Mediator of Fate-Decision of Adult Neural Stem Cells
TLDR
The possible use of DHA to impact NSPC fate-decision as a therapy for neurodegenerative diseases is introduced.
Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier
TLDR
It is demonstrated that Mfsd2a is essential for sphingosine-1-phosphate (S1P) export from endothelial cells in the brain and the findings help to unravel the mechanism by which S1P regulates BBB and also provide previously unidentified insights into the delivery of neurological drugs in the CNS.
Hepatic Levels of DHA-Containing Phospholipids Instruct SREBP1-Mediated Synthesis and Systemic Delivery of Polyunsaturated Fatty Acids
Structural basis of omega-3 fatty acid transport across the blood-brain barrier.
TLDR
The structure of MFSD2A is determined using single-particle cryo-electron microscopy, which reveals twelve transmembrane helices that are separated into two pseudosymmetric domains that provide insights into the molecular mechanism by which this atypical major facility superfamily transporter mediates the uptake of lysolipids into the brain.
The Role of Mfsd2a in Nervous System Diseases
TLDR
The physiological functions of Mfsd2a in the occurrence and development of intracranial hemorrhage (ICH), Alzheimer’s disease (AD), sepsis-associated encephalopathy (SAE), autosomal recessive primary microcephaly (MCPH) and intrac Cranial tumor are summarized.
Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4
Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease.
  • R. Semba
  • Biology, Psychology
    Advances in nutrition
  • 2020
TLDR
The LPC pathway is a promising area for future investigators to identify modifiable risk factors for AD and potentially limit the supply of long-chain fatty acids to the brain, including PUFAs such as DHA, and play a role in the pathobiology of AD.
Docosahexaenoic acid,22:6n-3: Its roles in the structure and function of the brain
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