Researchers from the David Geffen UCLA School of Medicine, the Howard Hughes UCLA Medical Institute, and the National Institutes of Health have developed a zebrafish model that provides new insight into how the brain acquires omega-3 essential fatty acids. , including docosahexaenoic acid (DHA). and linolenic acid (ALA). Their findings, published in nature communications, have the potential to improve understanding of lipid transport across the blood-brain barrier and disruptions in this process that can lead to birth defects or neurological conditions. The model may also allow researchers to design drug molecules that are capable of reaching the brain directly.
Omega-3 fatty acids are considered essential because the body cannot make them and must be obtained through food, such as fish, nuts, and seeds. DHA levels are especially high in the brain and are important for a healthy nervous system. Babies obtain DHA from breast milk or formula, and deficiencies in this fatty acid have been linked to learning and memory problems. To reach the brain, omega-3 fatty acids must cross the blood-brain barrier via the lipid transporter Mfsd2a, which is essential for normal brain development. Despite its importance, scientists did not know precisely how Mfsd2a transports DHA and other omega-3 fatty acids.
In the study, the research team provides images of the structure of the Mfsd2a zebrafish, which is similar to its human counterpart. The snapshots are the first to accurately detail how fatty acids move across the cell membrane. The study team also identified three compartments in Mfsd2a that suggest distinct steps required to move and flip fatty acids through the transporter, as opposed to moving through a linear tunnel or along the surface of the protein complex. The findings provide key information about how Mfsd2a transports omega-3 fatty acids to the brain and may allow researchers to optimize drug delivery via this pathway. The study also provides fundamental insights into how other members of this family of transporters, called the major facilitator superfamily (MFS), regulate important cellular functions.
The study was led by Tamir Gonen, Ph.D., of UCLA and Doreen Matthies, Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The NIH’s National Institute of General Medical Sciences (NIGMS) and the Howard Hughes Medical Institute provided additional funding for the study.
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