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

Author(s)

Ana Paula Pinto

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2021-09-28

Examining board members

Adelino Sanchez Ramos da Silva; Fábio Santos de Lira; Camila de Moraes; Hugo Celso Dutra de Souza

• Advisor: Adelino Sanchez Ramos da Silva

Abstract

The excessive eccentric exercise led to hepatic fat accumulation, which occurred concomitantly with elevation in the main proteins of the mammalian target of the rapamycin complex 1 (mTORC1) and insulin signaling pathways. Since mTORC1 and insulin can inhibit the autophagy pathway and explain the liver lipid content elevation, the main objective of the present investigation was to verify the responses of genes and proteins related to the autophagy and lipogenesis pathways in the hepatic tissue of mice submitted to the excessive downhill running protocol with and without rapamycin administration, a drug able to inhibit the mTORC1 pathway. C57BL/6 mice were divided into four experimental groups: Control (CT; sedentary), Excessive exercise in downhill running (EE), Excessive exercise in downhill running with chronic administration of rapamycin (EE/Rapa), and Endurance exercise (END). At the end of the 8-week protocols, the blood and liver were collected for serum analysis, histology, immunohistochemistry, hepatic fat content, reverse transcription-quantitative polymerase chain reaction, and immunoblotting. The main results were: 1) higher levels of glucose, insulin, HOMA-IR, cortisol, ALT, and cholesterol, but lower levels of T4 for the EE/Rapa group; 2) hepatic fat accumulation for the EE and EE/Rapa groups; 3) upregulation of LC3 immunoexpression and downregulation of autophagic genes for the EE, EE/Rapa, and END groups; 4) reduction of p70S6K phosphorylation and increase of Foxo1A phosphorylation for the EE/Rapa group. In summary, excessive exercise in downhill running with or without rapamycin led to increased liver fat content. Although rapamycin was effective in inhibiting mTOR, the autophagy pathway was not upregulated. (AU)

• FAPESP's process: 17/19869-8 - Molecular mechanisms related to increased hepatic fat content in response to excessive physical exercise
• Grantee: Ana Paula Pinto
• Support Opportunities: Scholarships in Brazil - Doctorate