Rapamycin did not prevent the excessive exercise-induced hepatic fat accumulation

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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. ; Quadrilatero, Joe ; da Silva, Adelino S. R.

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 306, p. 12-pg., 2022-07-15.

Resumo

Aims: The excessive eccentric exercise led to hepatic fat accumulation, which occurred concomitantly with elevation in 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. Main methods: C57BL/6J 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 protocols, the blood and liver were collected for serum analysis, histology, immunohistochemistry, hepatic fat content, reverse transcription -quantitative polymerase chain reaction, and immunoblotting. Key findings: 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 flux index for the EE and EE/Rapa groups; 4) reduction of P70S6K phosphorylation and SQSTM1 and increase of FOXO1A phosphorylation for the EE/Rapa group. Significance: The excessive exercise in downhill running with or without rapamycin led to increased liver fat content. Although rapamycin was effective in inhibiting mTORC1, the autophagy flux was not upregulated. (AU)

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