Brain uptake and utilization of fatty acids: recommendations for future research.

Abstract

A primary goal of the international workshop "Brain Uptake and Utilization of Fatty Acids" was to identify research areas that would benefit from further investigation. The major themes for future research are presented below: (1) Elucidating the role of the developing and mature cerebrovascular endothelium (CVE) in the uptake of fatty acids (FA) into the brain. (2) Clarifying the role of diffusion and receptor-mediated uptake of FAs by various brain cell membranes and protein-mediated shuttling of FAs between the CVE and various brain cells and tissues. (3) Illuminating the mechanisms of intermediate metabolism and the roles of polyunsaturated fatty acids (PUFA) in astrocytes, neurons and oligodendrocytes. Of special interest are the long-chain omega-3 PUFA and their derivatives, such as lipoproteins, phospholipids and plasmalogens, that have been associated with various disease states (such as those listed in [5], below). (4) Elucidating the role of gene expression on long-chain omega-3 PUFA incorporation in membranes and the regulatory role these and other PUFA have on gene expression in the brain. (5) Elucidating the recently identified roles of long-chain omega-3 PUFA in mood disorders, schizophrenia, stroke, peroxisomal biogenesis disorders, Huntington's disease, other neurodegenerative disorders and disorders of oxidative stress. (6) Undertaking placebo-controlled clinical trials to assess the therapeutic potential of omega-3 PUFA in the above disorders. (7) Developing new, and utilizing existing animal models in the above studies. (8) Developing noninvasive imaging and tagging methods for quantifying the migration and distribution of PUFA and their derivatives in the brain. (9) Applying multi-disciplinary collaborations among biophysicists, physiologists and molecular biologists to the resolution of the above.