NUTRITION, LIPOPROTEIN LIPASE AND BODY WEIGHT REGULATION

描述(改编自申请者摘要)：研究将 测定：(1)合成脂蛋白脂酶(LPL)的细胞内 脊髓和周围神经以及LPL在这些区域的功能 网站。推测LPL是由脑内少突胶质细胞形成的。 脊髓和周围神经中的雪旺细胞，以及LPL在 神经系统的主要作用是促进 膜磷脂合成的脂肪酸；(2)膜磷脂合成机制 LPL蛋白在脑内的定位。据推测， LPL蛋白在毛细血管内皮细胞上的分布 大脑是脂肪酶通过循环传递的结果； (3)LPL在大脑中的功能，其中LPL 合成的。因为LPL mRNA已经定位于许多细胞 脑中的类型包括海马区的神经元、浦肯野细胞 在小脑和大脑皮层深处的细胞中， 脂解产物，即由LPL的作用产生的脂肪酸 在这些部位富含甘油三酯的脂蛋白上，会增强 膜兴奋性。虽然葡萄糖是主要的燃料， 最近的报告表明，中枢神经系统(CNS)的变化 下丘脑内的脂肪酸氧化反应能量的变化 平衡。此外，抑制脂肪酸氧化也会抑制摄食。 由于血浆富含甘油三酯的脂蛋白随着饲料的增加而增加，因此 LPL依赖的通路可能在某些脑区作为一种 发出饱足的信号。此外，通过甘油三酯进行的突触传递- 富含脂蛋白甘油三酯的脂肪酸可产生代谢 与体重调节有关的记忆。总体而言，这些研究 应该提供一个全面的方法来解释LPL的存在 在神经系统中。

DESCRIPTION (Adapted from Applicant's Abstract): 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.