Duke-NUS scientists make key 'brain fats' finding

People literally need to get fat in the brain to live a healthy life.

Scientists in Singapore have proven that a special type of fat is needed in the human brain for it to grow properly, a finding that could eventually pave the way for new treatments for various diseases.

The Duke-NUS Graduate Medical School researchers worked with others to show that the fats, called lysophosphatidylcholines or LPCs, are produced by the liver and then carried into the brain by a protein called Mfsd2a.

When they examined two families in Libya and Egypt with severely reduced brain sizes - a disease called microcephaly - they found that mutations in the protein were to blame.

The mutations eliminated the protein's ability to transport the LPCs, so the brains did not absorb enough of the fats, which the scientists believe are the building blocks of the human brain.

The children with the mutations died when they were between one and six years old.

In a second study, the scientists looked at a family in North Pakistan with a different Mfsd2a mutation. While this family's microcephaly was not lethal, the members had intellectual disabilities, less control of their limbs and could not speak.

Both studies were published last month in the online edition of the prestigious scientific journal Nature Genetics.

Duke-NUS Associate Professor David Silver said: "Our work proves the essential role of LPCs in brain development and function in people.

"We are now studying the functions of LPCs in the brain, and might be able to develop drugs in future to prevent and treat neurological diseases like Alzheimer's and Parkinson's, and improve brain growth and function."

He added that the work could shed light on how to provide better brain nutrition for babies, mothers and the elderly, and could aid in the fight against glioblastoma multiforme, a common and lethal form of brain cancer.

A blood brain barrier protects the brain from foreign substances in the blood, but it also prevents drugs for various diseases from reaching the brain.

Now that the scientists have found out how the Mfsd2s protein delivers LPCs into the brain, they can better design drugs that use LPCs as carriers to cross the barrier, Prof Silver said.

Still, more work is needed - the researchers do not know yet which LPCs are crucial for the brain's development. Prof Silver said there are more than 10 known major LPCs in human blood, and the researchers' work will include finding out more about each of their functions.

The studies were done with Rockefeller University in the United States and Britain's University of Exeter. The research was partly funded by the Singapore National Research Foundation.

This article was first published on June 15, 2015.
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