How Cells Transport Omega-3 Fats to Build Myelin in the Brain

This laboratory study in mice examined a protein called Mfsd2a, which acts as a transporter that pulls omega-3-containing lysolipids (a special form of fat) into cells. Earlier research found that people born without a working version of this transporter develop microcephaly (a smaller brain) and hypomyelination (thinner insulation around nerve fibers), but it wasn’t clear exactly how the transporter contributed to myelin formation.

The researchers found that Mfsd2a is highly active in oligodendrocyte precursor cells (OPCs), the cells that mature into myelin-producing cells in the brain. When they removed Mfsd2a specifically from these precursor cells in mice, the cells matured too early and then failed to fully develop into functional myelin-producing cells, leading to reduced myelin after birth. Interestingly, these mice did not develop microcephaly, suggesting that the small-brain effect seen in humans is linked to a different location—the blood-brain barrier—rather than to the precursor cells themselves.

Detailed lipid analysis showed that without Mfsd2a, these precursor cells had lower levels of omega-3-containing phospholipids and higher levels of other fats made through the body’s own internal fat-building pathway (governed by a molecule called Srebp-1). Gene activity tests confirmed this pathway was overactive, alongside disrupted expression of genes that normally guide oligodendrocyte development.