胰高血糖素样肽-1调控摄食与味觉的杏仁机制研究

Glucagon-like peptide-1 (GLP-1) has been becoming the hot spot for the researchers for its considerable food intake-suppressing and bodyweight-reducing effects.The central nucleus of the amygdala (CeA)plays an important role in regulating hedonic taste perception and feeding. This project is try to determine the roles of the CeA in GLP-1 modulating the taste perception and intake of sweet tastants and fat; to explore the possible roles and uderlying mechanisms of GLP-1 in the CeA in regulating taste sensation and the intake of sweet tasants and fat; to lluminate the possible relationship between GABAergic neurons and the GLP-1 in the CeA exerting the above regulatory roles; to study the intracellular signal pathway mediating the food intake-suppressive effects of GLP-1 in the CeA by using multidisciplinary apoaches including behavioral, neuropharmacological, immunohistochemical and biological methods. The results and conclusions will increase the understanding the central mechanisms underlyig food intake-suppressing effects of GLP-1, and will be helpful in prevention of and treatment for abnormal feeding and obesity with GLP-1 in the future.

胰高血糖素样肽-1（glucagon-like peptide-1，GLP-1）由于其厌食、降体重效应而成为当今研究者们关注的热点。杏仁中央核（the central nucleus of the amydala, CeA）在愉悦味觉感知和摄食调控中扮演重要角色。本研究拟应用行为学、神经药理学、形态学以及分子生物学方法，确定CeA在GLP-1调控甜味质和脂类物质摄入和味觉感受中的作用；揭示GLP-1在CeA内调控甜味质和脂类物质摄入和味觉感受的作用机制；分析GABA能神经元与GLP-1在杏仁水平调控甜味质和脂类物质摄入和味觉感受的相互联系；研究CeA内GLP-1系统抑制摄食的可能分子机制；为阐明GLP-1调控摄食的中枢机制提供有价值的、创新性研究资料，也为临床应用GLP-1干预/防治摄食行为异常和肥胖、糖尿病提供重要的理论依据。

应用行为学、神经药理学等研究方法，以杏仁中央核（CeA）假损毁、CeA损毁大鼠为研究对象，观察电损毁CeA后，胰高血糖素样肽-1（GLP-1）是否能继续发挥摄食抑制作用，证实CeA在GLP-1 抑制摄食行为中的作用，明确CeA在GLP-1介导的摄食抑制作用中所扮演的角色。研究结果提示，CeA在GLP-1介导的摄食抑制作用中扮演重要角色，电损毁CeA后，GLP-1不能继续发挥其摄食抑制作用。此外，进一步明确了饮食因素及遗传因素对大鼠蔗糖敏感性的影响；探讨了CeA内μ阿片受体调节大鼠蔗糖溶液摄入的具体机制；证实了腹侧被盖区的ghrelin信号通路能够同时调节奖赏饮食以及饥饿引起的过食行为。以上结果为阐明GLP-1调控摄食的中枢机制提供了有价值的研究资料，也为临床应用GLP-1干预/防治摄食行为异常和肥胖、糖尿病提供了重要的理论依据。今后将进一步研究CeA 内GLP-1 系统调制甜味质和脂肪食物的摄入行为的作用及CeA 内GABA 能神经元在其中的可能机制。