In vivo approaches and rationale for quantifying kinetics and imaging brain lipid metabolic pathways

Abstract

Developing a kinetic strategy to examine rates of lipid metabolic pathways can help to elucidate the roles that lipids play in tissue function and structure in health and disease. This review summarizes such a strategy, and shows how it has been applied to quantify different kinetic aspects of brain lipid metabolism in animals and humans. Methods involve injecting intravenously a radioactive or heavy isotope labeled substrate that will be incorporated into a lipid metabolic pathway, and using chemical analytical and/or imaging procedures (e.g., quantitative autoradiography or positron emission tomography) to determine tracer distribution in brain regions and their lipid compartments as a function of time. From the measurements, fluxes, turnover rates, half-lives and ATP consumption rates can be calculated, and incorporation rates can be imaged. Experimental changes in these kinetic parameters can help to identify changes in the expression of regulatory enzymes, and thus aid in drug targeting. Cases that are discussed are arachidonic acid turnover and imaging of neuroreceptor-initiated phospholipase A2 activation, ether phospholipid biosynthesis, and kinetics of the phosphatidylinositol cycle.