Role of kinin receptors in obesity and leptin signaling

激肽释放酶-激肽系统(KKS)是一种多肽激素系统，参与调节平滑肌收缩、内皮依赖性血管扩张、伤害性感觉和炎症反应。两个受体传递激肽B1和B2的作用。我们最近可以证明，激动素B1受体在瘦素信号传递中起着至关重要的作用，因此，B1缺陷小鼠对高脂饮食诱导的肥胖具有抵抗力。利用已建立和新产生的转基因和基因敲除小鼠模型，该项目计划阐明参与B1受体和瘦素相互作用的细胞类型，并进一步研究B2受体以及整个KKS在这些过程中的作用。最终目的是评估这两种激动素受体作为新的抗肥胖疗法的靶点。该项目由申请者小组与来自巴西圣保罗S联邦大学的Joǎo B.Pesquero教授小组共同实施。

The kallikrein-kinin system (KKS) is a peptide hormone system involved in the regulation of smooth muscle contraction, endothelium-dependent vasodilatation, nociception and inflammation. Two receptors transmit the actions of the kinin peptides, B1 and B2. We could recently show that the kinin B1 receptor is crucially involved in leptin signalling and, thus, B1 deficient mice were resistant to high fat diet induced obesity. Using established and newly generated transgenic and knockout mouse models, this project plans to clarify the cell types involved in the interactions between the B1 receptor and leptin, and further investigates the role of the B2 receptor as well as the whole KKS in these processes. The final aim is to evaluate the two kinin receptors as targets for novel anti-obesity therapeutics. The project is jointly performed by the group of the applicant together with the group of Prof. Joǎo B. Pesquero from the Federal University of Sǎo Paulo, Brazil.