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Molecular mechanisms related to increased hepatic fat content in response to excessive physical exercise

Grant number: 17/19869-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2018
Status:Discontinued
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Adelino Sanchez Ramos da Silva
Grantee:Ana Paula Pinto
Home Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):19/15428-2 - Role of autophagy in muscle stem cell differentiation, BE.EP.DR

Abstract

The association between Excessive Physical Exercise (EPE) and inadequate recovery is related to the increase in the major proteins of the mammalian target of rapamycin complex 1 (mTORC1), induction of signs of cellular edema, acute inflammation, and accumulation of fat in the hepatic tissue of mice. However, the EPE model based on chronic downhill running sessions (EPE/down) was also able to improve the major proteins involved in the hepatic insulin signaling. Since the molecular pathways of mTORC1 and insulin are associated with the inhibition of the autophagy pathway, the main objective of this research project will be to verify whether the increased of mTORC1 signaling pathway is associated with inhibition of autophagy, which would justify the increased fat content in the liver of the animals in response to the EPE/down model. In addition, we will use a group of mice that will be submitted to the EPE/down protocol and will receive chronic administration of rapamycin, a drug that inhibits the mTORC1 signaling pathway and is also capable of stimulating autophagy. This group will enable us to verify if the increase in liver fat content occurred predominantly due to activation of the mTORC1 pathway and inhibition of the autophagy pathway. (AU)

Scientific publications (4)
(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)
PINTO, ANA P.; DA ROCHA, ALISSON L.; CABRERA, ELISA M. B.; MARAFON, BRUNO B.; KOHAMA, EIKE B.; ROVINA, RAFAEL L.; SIMABUCO, FERNANDO M.; BUENO JUNIOR, CARLOS R.; DE MOURA, LEANDRO P.; PAULI, JOSE R.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DA SILVA, ADELINO S. R. Role of interleukin-6 in inhibiting hepatic autophagy markers in exercised mice. CYTOKINE, v. 130, JUN 2020. Web of Science Citations: 0.
DE VICENTE, LARISSA G.; PINTO, ANA P.; MUNOZ, VITOR R.; ROVINA, RAFAEL L.; DA ROCHA, ALISSON L.; GASPAR, RAFAEL C.; DA SILVA, LILIAN E. C. M.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DA SILVA, ADELINO S. R. Tlr4 participates in the responses of markers of apoptosis, inflammation, and ER stress to different acute exercise intensities in mice hearts. Life Sciences, v. 240, JAN 1 2020. Web of Science Citations: 0.
DA ROCHA, ALISSON L.; PINTO, ANA P.; KOHAMA, EIKE B.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DA SILVA, ADELINO S. R. The proinflammatory effects of chronic excessive exercise. CYTOKINE, v. 119, p. 57-61, JUL 2019. Web of Science Citations: 4.
PINTO, ANA P.; DA ROCHA, ALISSON L.; KOHAMA, EIKE B.; GASPAR, RAFAEL C.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; DE MOURA, LEANDRO P.; PAULI, JOSE R.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DE FREITAS, ELLEN C.; DA SILVA, ADELINO S. R. Exhaustive acute exercise-induced ER stress is attenuated in IL-6-knockout mice. Journal of Endocrinology, v. 240, n. 2, p. 181-193, FEB 2019. Web of Science Citations: 1.

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