A role for lipoprotein lipase in mesolimbic function

脂蛋白脂肪酶在中脑边缘功能中的作用

基本信息

批准号：
8720294
负责人：
RALPH J DILEONE
金额：
$ 22.14万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8720294
关键词：
Affect Area Behavior Brain Brain region Chylomicrons Cocaine Communication Data Diet Dopamine Drug Addiction Eating Enzymes Exposure to Fatty Acids Fatty acid glycerol esters Feeding behaviors Food Hormones Hypothalamic structure Label Leptin Lipase Lipoproteins Locomotion Maps Measures Mediating Messenger RNA Metabolic Metabolism Midbrain structure Motivation Neurons Neurophysiology - biologic function Nucleus Accumbens Obesity Pathway interactions Pharmaceutical Preparations Process Proteins Psychological reinforcement Regulation Rewards Role Signal Transduction System Testing Triglycerides Ventral Tegmental Area Work addiction attenuation behavior influence brain pathway drug of abuse feeding lipoprotein lipase neural circuit neurochemistry novel particle public health relevance research study response therapeutic development uptake

项目摘要

DESCRIPTION (provided by applicant): Metabolic factors can act directly on the brain to influence neural function and relevant behaviors. While several of these signals (e.g. leptin) are known and studied, there are likely to be many other signals in the form of metabolites. The identification of a key fat metabolic enzyme, lipoprotein lipase (LPL) in dopamine centers of the brain raises the intriguing possibility that these areas are influenced by triglycerides. This woul have implications for many behaviors influenced by dopamine, including food intake and drug addiction. Preliminary data suggests that LPL functions in the nucleus accumbens (NAc) to influence food intake. The present proposal seeks to characterize the expression and regulation of LPL in these centers while also determining the function of the lipase in both the nucleus accumbens as well as the ventral tegmental area (VTA). Both feeding and response to drugs of abuse will be measured to gain a more complete appreciation of the function of LPL in the regions. The proposed work is important for giving us an integrated picture of metabolic signaling to the brain, while also generating novel pathways for therapeutic development for obesity and addiction.

描述（由申请人提供）：代谢因素可以直接作用于大脑，影响神经功能和相关行为。虽然其中一些信号（例如瘦素）是已知和研究的，但可能还有许多其他以代谢物形式存在的信号。在大脑多巴胺中心发现了一种关键的脂肪代谢酶——脂蛋白脂肪酶（LPL），这提出了一个有趣的可能性，即这些区域受到甘油三酯的影响。这将对受多巴胺影响的许多行为产生影响，包括食物摄入和药物成瘾。初步数据表明，LPL 在伏隔核 (NAc) 中发挥作用，影响食物摄入。本提案旨在描述这些中心 LPL 的表达和调节特征，同时确定伏隔核和腹侧被盖区 (VTA) 中脂肪酶的功能。将测量喂养和对滥用药物的反应，以便更全面地了解 LPL 在这些地区的功能。这项工作对于让我们全面了解大脑代谢信号传导非常重要，同时也为肥胖和成瘾的治疗开发提供了新的途径。