Offspring from trained male mice inherit improved muscle mitochondrial function through PPAR co-repressor modulation

Author(s):Show less -

Freitas-Dias, Ricardo ; Lima, Tanes, I ; Costa-Junior, Jose Maria ; Goncalves, Luciana M. ; Araujo, Hygor N. ; Paula, Flavia M. M. ; Santos, Gustavo J. ; Souto Branco, Renato Chaves ; Ou, Kristy ; Kaestner, Klaus H. ; Silveira, Leonardo R. ; Oliveira, Camila A. M. ; Boschero, Antonio C. ; Zoppi, Claudio C. ; Carneiro, Everardo M.

• Document type: Journal article
• Source: Life Sciences; v. 291, p. 8-pg., 2022-02-15.

Abstract

Aim Investigate whether inheritance of improved skeletal muscle mitochondrial function and its association with glycemic control are multigenerational benefits of exercise. Main methods: Male Swiss mice were subjected to 8 weeks of endurance training and mated with untrained females. Key findings: Trained fathers displayed typical endurance training-induced adaptations. Remarkably, offspring from trained fathers also exhibited higher endurance performance, mitochondrial oxygen consumption, glucose tolerance and insulin sensitivity. However, PGC-1 alpha expression was not increased in the offspring. In the offspring, the expression of the co-repressor NCoR1 was reduced, increasing activation of PGC-1 alpha target genes. These ef-fects correlated with higher DNA methylation at the NCoR1 promoter in both, the sperm of trained fathers and in the skeletal muscle of their offspring. Significance: Higher skeletal muscle mitochondrial function is inherited by epigenetic de-activation of a key PGC-1 alpha co-repressor. (AU)

• FAPESP's process: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass
• Grantee: Antonio Carlos Boschiero
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/01717-9 - Investigation of the insulinotropic, insulinomimetic and endothelial actions of taurine in cells/tissues submitted to an in vitro amino acid restriction: an integrated and multifocal approach
• Grantee: Everardo Magalhães Carneiro
• Support Opportunities: Research Projects - Thematic Grants