Researchers at the UCLA David Geffen School of Medicine, the Howard Hughes Medical Institute at UCLA and the National Institutes of Health have developed a zebrafish model that provides new insight into how the brain obtains essential omega-3 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 able to directly target the brain.
Omega-3 fatty acids are considered essential because the body cannot make them and must obtain them from foods such as fish, nuts and seeds. DHA levels are particularly high in the brain and are important for a healthy nervous system.
Infants obtain DHA from breast milk or formula, and a deficiency of this fatty acid is 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.
DHA and other omega-3 fatty acids
Despite its importance, scientists did not know exactly how Mfsd2a transports DHA and other omega-3 fatty acids. In the study, the research team provides images of the structure of zebrafish Mfsd2a, which is similar to its human counterpart. The images are the first to accurately describe how fatty acids move across a 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 into the brain and may allow researchers to optimize drug delivery through this pathway. The study also provides fundamental knowledge of 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 the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Additional funding for the study was provided by the NIH’s National Institute of General Medical Sciences (NIGMS) and the Howard Hughes Medical Institute.
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