权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Neuronal GPR149 and energy homeostasis

神经元 GPR149 和能量稳态

基本信息

批准号：
10216693
负责人：
Laurent Gautron
金额：
$ 16.38万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10216693
关键词：
Adrenal Glands Afferent Neurons Anatomy Antibodies Body Weight Brain CRISPR/Cas technology Cells Chronic Cues Data Development Diabetes Mellitus Diagnostic tests Disease Drug Targeting Eating Energy Metabolism Fasting Female Food Energy Future G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs Glucose Grant Hand Hepatic Homeostasis Hypothalamic structure In Situ Hybridization Incidence Laboratories Lead Link Lipids LoxP-flanked allele Metabolic Metabolic Diseases Molecular Mus Nervous system structure Neural Pathways Neuraxis Neurons Obesity Orphan Pattern Peripheral Peripheral Nervous System Pharmacologic Substance Physiological Pituitary Gland Prevention strategy Production Regulation Research Research Personnel Role Scientist Signal Transduction Thyroid Gland Time Tissues Validation Work blood glucose regulation cell type cohort data sharing design diet-induced obesity energy balance feeding interest mRNA Expression male mouse model neuroregulation novel nutrition receptor response systemic inflammatory response web portal

项目摘要

PROJECT SUMMARY/ABSTRACT The incidence of obesity and related disorders including diabetes mellitus continue to rise. Chronic over nutrition is prevalent, which has profound metabolic effects including causing increased systemic inflammation and altered hepatic glucose and lipid production. Research into the molecular mechanisms underlying energy balance are important for developing new prevention strategies, diagnostic tests and treatments in chronic metabolic diseases such as obesity and diabetes. Notably, our emphasis on a G-protein coupled receptor (GPCR) may lead to the development of novel pharmaceutical therapies, as these are currently the most heavily investigated receptor groups for drug target development. Specifically, GPR149 is an orphan GPCR about which very little is known in terms of body distribution and physiological role(s). However, our laboratory has recently found that Gpr149 is highly expressed in a brain circuit involved in the regulation of energy homeostasis and feeding. Hence, our data support the hypothesis that neuronal GPR149 links an unknown metabolic cue to the neural pathways controlling energy homeostasis. Notably, using the CRISPR-Cas9 technology, we have generated a novel mouse model allowing the deletion of endogenous Gpr149 expression in a tissue-specific manner. Using this mouse model, our proposal will directly assess the physiological role of neuronal GPR149 in energy balance. Ultimately, the data generated under this RFA will be findable through Pharos and serve as a basis for future efforts aimed at understanding the basic role of GPR149 signaling.

项目概要/摘要肥胖和包括糖尿病在内的相关疾病的发病率持续上升。慢性结束营养很普遍，具有深远的代谢影响，包括导致全身炎症增加并改变肝脏葡萄糖和脂质的产生。研究能量背后的分子机制平衡对于制定慢性病的新预防策略、诊断测试和治疗非常重要代谢性疾病，例如肥胖和糖尿病。值得注意的是，我们强调 G 蛋白偶联受体（GPCR）可能会导致新型药物疗法的开发，因为这些疗法是目前最有效的深入研究了药物靶标开发的受体组。具体来说，GPR149 是一个孤儿 GPCR 关于其身体分布和生理作用知之甚少。然而，我们的实验室最近发现Gpr149在参与能量调节的脑回路中高表达体内平衡和喂养。因此，我们的数据支持神经元 GPR149 连接未知的假设控制能量稳态的神经通路的代谢线索。值得注意的是，使用 CRISPR-Cas9 技术，我们生成了一种新的小鼠模型，允许删除内源性 Gpr149 表达以组织特异性的方式。使用该小鼠模型，我们的建议将直接评估能量平衡中的神经元 GPR149。最终，根据本 RFA 生成的数据将可以通过 Pharos 并作为未来旨在了解 GPR149 信号传导基本作用的努力的基础。