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Kinin receptors in the adipose tissue

Grant number: 08/54904-0
Support Opportunities:Regular Research Grants
Duration: January 01, 2009 - December 31, 2010
Field of knowledge:Biological Sciences - Biology
Convênio/Acordo: INSERM
Principal Investigator:João Bosco Pesquero
Grantee:João Bosco Pesquero
Principal researcher abroad: Jean-Loup Bascands
Institution abroad: Institut National de la Santé et de la Recherche Médicale (Inserm), France
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Kinins activate two G-protein coupled receptors: the B2 receptor (B2R) which is expressed in physiological conditions and the B1 receptor(BIR) which is mainly induced under inflammatory conditions. Besides the classical well known functions of kinin receptors such as vasodilation, extravasation, pain, hyperalgesia and their roles in inflammation, we have recently observed that B1R knock-out mice are rather tolerant to lipid-rich-diet-induced obesity. On the other hand we observed that B1R knock-out mice have both low white adipose leptin mRNA and plasmatic leptin level. Finally intravenous B1R-agonist administration increased the leptin plasmatic concentration. Those exciting preliminary data suggest that the B1R is involved in the control of plasma leptin levels although no clear mechanism nor physiological function for the B1R in adipose tissue has been proposed. Interestingly it has been reported by Shiuchi et al (Endocrinol, 2001) that the B2R was involved in leptin-induced glucose uptake. Taken together it appears that a new function for kinin receptors in obesity is emerging but needs to be confirmed by additional data. Thus our project aims to determine how the kinin receptors modify or contribute to the functionality of adipocytes. This project should help to determine whether kinin receptors can become targets in anti-obesity therapy. (AU)

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