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Kallikrein kinin system in physical exercise and metabolism

Grant number: 15/20082-7
Support type:Research Projects - Thematic Grants
Duration: November 01, 2016 - October 31, 2021
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Ronaldo de Carvalho Araújo
Grantee:Ronaldo de Carvalho Araújo
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Alexandre Budu ; Maria Do Carmo Pinho Franco ; Sandro Soares de Almeida ; Silvia Daher
Associated grant(s):17/10126-2 - Multi-center equipment approved in grant 2015/20082-7, AP.EMU
16/24721-7 - Multi user equipment from process 2015/20082-7 PCR real time machine, AP.EMU
Associated scholarship(s):18/05880-2 - Modulation of the renal inflammatory process by the inhibition of B1 receptors of kinins in immunological cells, BP.IC
17/21368-7 - Role of kinin B1 receptor in maternal metabolism induced by physical training during the pregnancy, BP.DD
17/08361-3 - Evaluating recreational physical exercise, birth weight, pressure levels and components of renin-angiotensin-kallikrein-kinin system interactions in children, BP.PD


The kallikrein-kinin system (KKS) participates in inflammatory processes, pain mediation and control of blood pressure. Recent evidences suggest the involvement of this system in the modulation of physical exercise, metabolism and obesity. Such involvement could be partly mediated by interaction with the immune system, with glycemic control and cardiovascular homeostasis. To evaluate the role of kallikrein kinin system in metabolism and physical exercise, we'll use genetically modified animals for that system generated by our group. In humans, we'll evaluate the polymorphisms of the components of KKS as well as the activities of KKS and metabolic enzymes and/or vascular effects. Recently my group showed a role of kinin B2 receptor in hepatic gluconeogenesis in obese animals. However, modulation of training and degrading liver glycogen enzymes have not been investigated and it will be evaluated by their gene expression and its activities. The possible impact of these phenomena in physical exercise will also be assessed. To this end, deficient animals for the kinin receptors (B1KO, B2KO and B1B2KO) will be subjected to strenuous acute physical exercise, a practice in which liver glycogen is the main energy source. Evaluation of kinin B1 receptor with IL-6 transignaling, molecule released by exercise, and that has an important role in the metabolism and immune system will be investigated. To show the relationship between inflammatory processes, toll like receptors and exercise, deficient mice for kinin receptors will be submitted to physical training programs. Then these animals will undergo treatments to increased inflammation. Changes in KKS is associated with preeclampsia, a disorder that occurs during pregnancy where the process of angiogenesis is impaired. The reduction of the kallikrein activity is observed in hypertension and restriction of intrauterine growth in pregnancy. The reduction of the expression of B1R gene in placentas of women with preeclampsia strongly supports the inclusion of KSS studies on vascular growth. On the other hand it is known that the activation of the KSS after exercise. So we intend to evaluate the impact of kinin receptors in fetal growth and placental function in animals subjected to physical exercise during pregnancy. It is known that placental changes that induce a lower supply of nutrients to the fetus can modulate a low birth weight and this factor is an important marker of future chronic diseases. So we intend to evaluate, in humans, the mechanisms related to the KKS involved in development of chronic diseases related to low birth weight as well as the beneficial role of physical training. We'll evaluate before and after 12 weeks of intervention with physical training in children and adolescents aged 6 to 14 years. We published in 2010 that obese adolescents submitted to a food control and exercise program responded differently, being correlated with the polymorphism of insertion / deletion (I / D) of 287 bp in intron 17 of the ACE gene, one of the components KKS. One of the sub-projects of this thematic seeks to track those children (now adults) and assess whether polymorphisms in the KKS (I / D ACE and +9 / -9 receptor B2) are associated with adherence to the program and the maintenance of body weight and their relationship of polymorphisms with the current metabolic variables. (AU)

Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MALVEIRA CAVALCANTE, PAULA ANDREA; ALENINA, NATALIA; BUDU, ALEXANDRE; FREITAS-LIMA, LEANDRO CEOTTO; ALVES-SILVA, THAIS; HENAO AGUDELO, JUAN SEBASTIAN; QADRI, FATIMUNNISA; SARAIVA CAMARA, NIELS OLSEN; BADER, MICHAEL; ARAUJO, RONALDO CARVALHO. Nephropathy in Hypertensive Animals Is Linked to M2 Macrophages and Increased Expression of the YM1/Chi3l3 Protein. Mediators of Inflammation, v. 2019, JUL 10 2019. Web of Science Citations: 0.
WASINSKI, FREDERICK; BATISTA, ROGERIO OLIVEIRA; BADER, MICHAEL; ARAUJO, RONALDO C.; KLEMPIN, FRIEDERIKE. Bradykinin B2 receptor is essential to running-induced cell proliferation in the adult mouse hippocampus. Brain Structure & Function, v. 223, n. 8, p. 3901-3907, NOV 2018. Web of Science Citations: 1.
MAFRA, FERNANDO F. P.; GATTAI, PEDRO P.; MACEDO, MICHEL M.; MORI, MARCELO A.; ARAUJO, RONALDO C. The angiotensin-I-converting enzyme insertion/deletion in polymorphic element codes for an AluYa5 RNA that downregulates gene expression. PHARMACOGENOMICS JOURNAL, v. 18, n. 4, p. 517-527, JUL 2018. Web of Science Citations: 0.
ALMEIDA, SANDRO S.; CORGOSINHO, FLAVIA C.; AMORIM, CARLOS E. N.; GREGNANI, MARCOS F.; CAMPOS, RAQUEL M. S.; MASQUIO, DEBORAH C. L.; SANCHES, PRISCILA L.; GANEN, ALINE P.; PESQUERO, JOAO B.; DAMASO, ANA R.; MELLO, MARCO T.; TUFIK, SERGIO; ARAUJO, RONALDO C. Different metabolic responses induced by long-term interdisciplinary therapy in obese adolescents related to ACE I/D polymorphism. JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, v. 18, n. 2 APR-JUN 2017. Web of Science Citations: 1.
ESTRELA, GABRIEL R.; WASINSKI, FREDERICK; FELIZARDO, RAPHAEL J. F.; SOUZA, LAURA L.; CAMARA, NIELS O. S.; BADER, MICHAEL; ARAUJO, RONALDO C. MATE-1 modulation by kinin B1 receptor enhances cisplatin efflux from renal cells. Molecular and Cellular Biochemistry, v. 428, n. 1-2, p. 101-108, APR 2017. Web of Science Citations: 3.
ESTRELA, GABRIEL R.; WASINSKI, FREDERICK; BATISTA, ROGERIO O.; HIYANE, MEIRE I.; FELIZARDO, RAPHAEL J. F.; CUNHA, FLAVIA; DE ALMEIDA, DANILO C.; MALHEIROS, DENISE M. A. C.; CAMARA, NIELS O. S.; BARROS, CARLOS C.; BADER, MICHAEL; ARAUJO, RONALDO C. Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation. FRONTIERS IN PHYSIOLOGY, v. 8, MAR 2 2017. Web of Science Citations: 4.

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