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Effects of fasting and strength physical exercise on the AMPK / TBK1 signaling pathway in the liver of obese and diabetic mice

Grant number: 21/00880-7
Support Opportunities:Regular Research Grants
Duration: March 01, 2022 - February 29, 2024
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Leandro Pereira de Moura
Grantee:Leandro Pereira de Moura
Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Associated researchers:Célio Junior da Costa Fernandes ; Fernando Moreira Simabuco


Obesity is a global public health problem. Unfortunately, up to date, beyond caloric restriction and regular exercise practice, there is no safe strategy to reduce its complications. Both practices have as a common action the increase of AMPK activity which in turn can increase the glucose uptake and fat oxidation and reduce hepatic inflammation and non-alcoholic steatohepatitis. Factors that activate this molecule are known. However, the molecules that are activated by AMPK are still little explored. Therefore, knowing the downstream mechanisms of this protein is of paramount importance for understanding how AMPK can contribute to the treatment or prevention of obesity and related diseases. In this sense, TBK1 protein, a downstream molecule of AMPK, has recently been listed as an important molecule that reduces the inflammatory profile in the obesity condition. TBK1 is activated by the AMPK/ULK-1 pathway in peripheral tissues. Once activated, it is capable of stimulating the degradation of NIK, thereby reducing its association with TRAF2 and IKK± phosphorylation and the displacement of the NF-ºB complex (p52/RelB) from the cell nucleus and, thus, reducing the transcription of inflammatory factors. Therefore, because the effects of caloric restriction and physical strength exercise are known in the phosphorylation of AMPK, but little explored, it becomes important to understand if these two strategies modulate downstream signaling from this molecule, such as the TBK1. At the end of this study, it is expected to understand whether the benefits of fasting and strength physical exercise on AMPK activity are mediated by TBK1 signaling. Therefore, the objective of this study is to investigate how fasting and physical strength exercise can modulate the TBK1 and consequently the translocation of NF-kB to the cell nucleus. If the hypothesis of the present study is confirmed, just as AMPK is highly indicated as an important target protein to be regulated, TBK1 may also be listed as a further target protein for the control of hepatic inflammation, non-alcoholic steatohepatitis, and consequently diabetes mellitus. Thus, new strategies can be thought for the modulation of TBK1. (AU)

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Scientific publications
(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)
FERNANDES, CELIO JUNIOR DA COSTA; RODRIGUES, KELLEN CRISTINA DA CRUZ; DE MELO, DIEGO GOMES; DE CAMPOS, THAIS DANTIS PEREIRA; CANCIGLIERI, RAPHAEL DOS SANTOS; SIMABUCO, FERNANDO MOREIRA; DA SILVA, ADELINO SANCHEZ RAMOS; CINTRA, DENNYS ESPER; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO; et al. Short-term strength exercise reduces the macrophage M1/M2 ratio in white adipose tissue of obese animals. Life Sciences, v. 329, p. 10-pg., . (21/00880-7, 21/02541-5, 19/16012-4)

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