EFFECTS OF REGULAR PHYSICAL EXERCISE AND OVERTRAINING ON THE BEHAVIOR OF THE AUTOPHAGIC PATHWAY IN DIFFERENT TISSUES OF MICE.

• Grant number: 17/09038-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2018
• End date: January 31, 2020
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Adelino Sanchez Ramos da Silva
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Giovana Rampazzo Teixeira ; José Rodrigo Pauli
• Associated research grant(s): 19/00137-2 - Effects of physical exercise on the autophagy pathway, AP.R SPRINT
• Associated scholarship(s): 19/10875-0 - Effects of regular physical exercise and overtraining on the behavior of the autophagic pathway in different tissues of mice, BP.TT; 18/03872-2 - Effects of regular physical exercise and overtraining on the behavior of the autophagic pathway in different tissues of mice, BP.TT

Abstract

The imbalance between excessive training and inadequate recovery periods is linked to the performance decrement and to the states of functional overreaching (FOR), nonfunctional overreaching (NFOR) and/or overtraining syndrome (OTS). Mice submitted to an overtraining protocol (OT) based on chronic eccentric exercise sessions (OTR/down) showed hepatic activation of the mTORC1 pathway and increase of the AMPK (Thr172). In the heart tissue, both mTOR (Ser2448) and AMPK (Thr172) were inhibited. In the EDL, while the mTORC1 pathway was inhibited, the AMPK (Thr172) was not modulated. Knowing that the AMPK and mTOR pathway are respectively related to the activation and inhibition of the autophagic pathway, the main aim of this research project will be to compare the responses of the proteins related to the autophagic pathway in the liver, heart and EDL after the OTR/down protocol with other three physical exercise protocols, an aerobic (AER group) with predominant activation of the AMPK pathway, an resistance (FO group) with predominant activation of the mTOR pathway, and an concurrent (CR group). Mice will be divided into 8 experimental groups and the project will present two stages. The following methodologies will be used: immunoblotting, real-time polymerase chain reaction (qPCR), histology, immunohistochemistry, immunofluorescence, bioinformatics analysis and autophagic flow analysis. According to the statistical data distribution, parametric or nonparametric tests will be used to compare the investigated parameters between the experimental groups. The level of significance of pd0.05 will be adopted. (AU)

Scientific publications

(16)

(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)

DE VICENTE, LARISSA G.; PINTO, ANA PAULA; DA ROCHA, ALISSON LUIZ; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DA SILVA, ADELINO S. R.. Role of TLR4 in physical exercise and cardiovascular diseases. CYTOKINE, v. 136, DEC 2020. (17/09038-1)

PINTO, ANA P.; VIEIRA, TALES S.; MARAFON, BRUNO B.; BATITUCCI, GABRIELA; CABRERA, ELISA M. B.; DA ROCHA, ALISSON L.; KOHAMA, EIKE B.; RODRIGUES, KELLEN C. C.; DE MOURA, LEANDRO P.; PAULI, JOSE R.; et al. The Combination of Fasting, Acute Resistance Exercise, and Protein Ingestion Led to Different Responses of Autophagy Markers in Gastrocnemius and Liver Samples. NUTRIENTS, v. 12, n. 3, MAR 2020. (17/09038-1)

DA ROCHA, ALISSON L.; ROVINA, RAFAEL L.; PINTO, ANA P.; MARAFON, BRUNO B.; DA SILVA, LILIAN E. C. M.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; et al. Interleukin-6 ablation does not alter morphofunctional heart characteristics but modulates physiological and inflammatory markers after strenuous exercise. CYTOKINE, v. 142, p. 11-pg., 2021-03-23. (19/17058-8, 17/09038-1, 17/17646-1, 19/00855-2)

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.; et al. Role of interleukin-6 in inhibiting hepatic autophagy markers in exercised mice. CYTOKINE, v. 130, JUN 2020. (17/09038-1, 18/14818-9, 18/12519-4, 17/19869-8, 17/12765-2, 19/10875-0)

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. (12/23258-0, 13/19985-7, 17/12765-2, 14/25459-9, 10/08239-4, 13/22737-5, 15/08013-0, 13/20591-3, 17/19869-8, 11/02652-0, 17/09038-1)

PINTO, ANA P.; DA ROCHA, ALISSON L.; TEIXEIRA, GIOVANA R.; ROVINA, RAFAEL L.; VERAS, ALLICE S. C.; FRANTZ, FABIANI; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; et al. Rapamycin did not prevent the excessive exercise-induced hepatic fat accumulation. Life Sciences, v. 306, p. 12-pg., 2022-07-15. (17/12765-2, 19/17058-8, 17/09038-1, 19/00137-2, 19/15428-2, 17/19869-8)

PINTO, ANA P.; DA ROCHA, ALISSON L.; MARAFON, BRUNO B.; ROVINA, RAFAEL L.; MUNOZ, VITOR R.; DA SILVA, LILIAN E. C. M.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; et al. Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 5, MAR 2021. (17/09038-1, 17/19869-8, 19/10875-0, 17/12765-2)

ROVINA, RAFAEL L.; PINTO, ANA P.; MUNOZ, VITOR R.; DA ROCHA, ALISSON L.; REBELO, MACARIO A.; TEIXEIRA, GIOVANA R.; TAVARES, MARIA EDUARDA A.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; et al. Genetic deletion of IL-6 increases CK-MB, a classic cardiac damage marker, and decreases UPRmt genes after exhaustive exercise. Cell Biochemistry and Function, v. 40, n. 4, p. 10-pg., 2022-04-12. (17/19869-8, 17/09038-1, 19/17058-8, 17/12765-2)

DA ROCHA, ALISSON L.; ROVINA, RAFAEL L.; PINTO, ANA P.; MARAFON, BRUNO B.; DA SILVA, LILIAN E. C. M.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; et al. nterleukin-6 ablation does not alter morphofunctional heart characteristics but modulates physiological and inflammatory markers after strenuous exercis. CYTOKINE, v. 142, JUN 2021. (19/17058-8, 17/17646-1, 17/09038-1, 19/00855-2)

ROVINA, RAFAEL L.; DA ROCHA, ALISSON L.; MARAFON, BRUNO B.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DA SILVA, ADELINO S. R.. One Bout of Aerobic Exercise Can Enhance the Expression of Nr1d1 in Oxidative Skeletal Muscle Samples. FRONTIERS IN PHYSIOLOGY, v. 12, FEB 1 2021. (17/12765-2, 18/12519-4, 17/09038-1)

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.; et al. 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. (12/13558-7, 17/09038-1, 18/14818-9, 18/12519-4, 17/19869-8, 17/12765-2)

DE VICENTE, LARISSA G.; MUNOZ, VITOR R.; PINTO, ANA P.; ROVINA, RAFAEL L.; DA ROCHA, ALISSON L.; MARAFON, BRUNO B.; DE A TAVARES, MARIA EDUARDA; TEIXEIRA, GIOVANA R.; FERRARI, GUSTAVO D.; ALBERICI, LUCIANE C.; et al. TLR4 deletion increases basal energy expenditure and attenuates heart apoptosis and ER stress but mitigates the training-induced cardiac function and performance improvement. Life Sciences, v. 285, NOV 15 2021. (20/04269-8, 17/09038-1)

DA ROCHA, ALISSON L.; PINTO, ANA P.; MORAIS, GUSTAVO P.; MARAFON, BRUNO B.; ROVINA, RAFAEL L.; VERAS, ALLICE S. C.; TEIXEIRA, GIOVANA R.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; et al. Moderate, but Not Excessive, Training Attenuates Autophagy Machinery in Metabolic Tissues. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 22, NOV 2020. (17/17646-1, 17/19869-8, 19/00855-2, 17/09038-1, 17/12765-2)

MORAIS, GUSTAVO PAROSCHI; DA ROCHA, ALISSON L.; NEAVE, LOUISE M.; LUCAS, GUILHERME DE A.; LEONARD, TIMOTHY R.; CARVALHO, ANDREA; DA SILVA, ADELINO SANCHEZ R.; HERZOG, WALTER. Chronic uphill and downhill exercise protocols do not lead to sarcomerogenesis in mouse skeletal muscle. JOURNAL OF BIOMECHANICS, v. 98, JAN 2 2020. (16/25766-4, 17/13251-2, 17/09038-1)

MARAFON, BRUNO BRIEDA; PINTO, ANA PAULA; DA ROCHA, ALISSON LUIZ; ROVINA, RAFAEL LEMES; PAULI, JOSE RODRIGO; DE MOURA, LEANDRO PEREIRA; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; RAMOS DA SILVA, ADELINO SANCHEZ. Hepatic LC3 II/I Ratio Is Not Modulated in Exercised Mice. Physiological Research, v. 69, n. 6, p. 1103-1111, DEC 2020. (17/09038-1, 19/10875-0)

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.; et al. 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. (17/19869-8, 12/13558-7, 17/12765-2, 17/09038-1)