Participation of the Kallikrein Kinin System in the Modulation of Metabolism and its Repercussion on Voluntary Activity and Physical Training.

• Grant number: 25/05631-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2025
• End date: May 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ronaldo de Carvalho Araújo
• Grantee: Clédia Silveira Flores da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/14313-7 - Role of kallikrein kinin system on metabolism and repercussion on voluntary exercise, AP.TEM

Abstract

Aiming at a better quality of life, physical activity and diet are essential factors that can be manipulated in an attempt to promote well-being and protection against various pathologies. Kinins, effector peptides of the kallikrein-kinin system (KKS), participate in inflammatory processes, in the mediation of pain and control of blood pressure and these effects are mediated by 2 types of G-protein coupled receptors, kinin receptor B1 and B2. Recent results from our group show the involvement of this system in the modulation of acute physical exercise, metabolism and obesity. The mechanisms related to such events suggest the interaction of kinins with molecules that modulate the glycemic profile and the immune system. The kinin receptor B1 plays an important role in glucose metabolism and it has been shown that animals deficient in this receptor present a decrease in insulin production, with an increase in sensitivity to this hormone. Our group also showed that they are sensitive to the administration of exogenous leptin, and that this must be related to their resistance to obesity. Another interesting finding that relates the role of the B1 receptor in metabolism was when the B1KO mice were challenged with a 48-hour fast. These animals presented approximately 1/3 of the serum concentrations of beta-hydroxybutyrate than those observed in wild-type animals. This suggests that lipid metabolism is impaired in these animals. Based on the data observed, we aim to evaluate whether these modifications can impact the response to voluntary activity, affect physical training performance, and which mechanism may be related to this effect. To this end, we will use transgenic animals for the SCC and pharmacological analyses with specific agonists and antagonists for the receptors. (AU)