A role for lipoprotein lipase in mesolimbic function

描述(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。虽然这些信号中的几个(例如瘦素)是已知和研究的，但很可能还有许多其他代谢物形式的信号。在大脑的多巴胺中心发现了一种关键的脂肪代谢酶，脂蛋白脂酶(LPL)，这提出了这些区域受到甘油三酯影响的有趣的可能性。这将对多巴胺影响的许多行为产生影响，包括食物摄取和药物成瘾。初步数据表明，LPL在伏隔核(NAC)发挥作用，影响食物的摄取。本研究试图确定LPL在这些中枢的表达和调控，同时还确定伏核和腹侧被盖区(VTA)中脂肪酶的功能。将对滥用药物的喂养和反应进行衡量，以更全面地了解LPL在该地区的作用。这项拟议的工作非常重要，它为我们提供了一幅向大脑传递代谢信号的综合图景，同时也为肥胖症和成瘾的治疗开发提供了新的途径。

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.