The studies will determine: (1) the cells of synthesis of lipoprotein lipase (LPL) within the spinal cord and peripheral nerve, and the function of LPL in these sites. It is postulated that LPL is made by oligodendrocytes in the spinal cord and by Schwann cells in peripheral nerve, and that LPL in the nervous system predominantly works to facilitate the provision of fatty acids for membrane phospholipid synthesis; (2) mechanisms for the localization of LPL protein in the brain. It is postulated that the distribution of LPL protein on the capillary endothelium throughout the brain is a consequence of delivery of the lipase by the circulation; and (3) the function of LPL in regions of the brain wherein LPL is synthesized. Because LPL mRNA has been localized to a number of cell types in the brain including neurons in the hippocampus, Purkinje cells of the cerebellum and cells deep within the cortex, it is postulated that lipolysis products, i.e. fatty acids, derived by the action of LPL on triglyceride-rich lipoproteins within these sites, will enhance membrane excitability. Although glucose is the predominant fuel for the central nervous system (CNS), recent reports indicate that changes in fatty acid oxidation within the hypothalamus reflect changes in energy balance. Moreover, inhibition of fatty acid oxidation inhibits feeding. Because plasma triglyceride-rich lipoproteins increase with feeding, an LPL-dependent pathway could function in certain brain regions as a signal for satiety. Moreover, synaptic transmission by triglyceride- rich lipoprotein triglyceride fatty acids could generate metabolic memory which relates to body weight regulation. Overall, these studies should provide a comprehensive approach to explain the presence of LPL in the nervous system.
