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The adaptations induced by Estrogen Related Receptor alpha (ERRα) disruption and exercise training on healthy and diabetic rat’s liver

Diabetes is a widespread metabolic disorder that needs specific management and researchers focused on exercise training and pharmacological interventions for diabetes management. Endurance training (ET) and ERRα gained attention as a potential therapeutic target for diabetes management. We investigated ET and ERRα inhibition effects on the expression of SIRT1 and AMPK in healthy and STZ-induced diabetic rats’ liver. Fifty-six Wistar rats were divided into 8 groups as follows (n = 7); group 1, control with no treatment; group 2, diabetic control group that received a single dose of STZ; group 3, ERRα inhibited group that received XCT 790; group 4, endurance training (ET); group 5, diabetic rats with ERRα inhibition; group 6, diabetic rats that performed ET; group 7, ERRα inhibition and ET; and group 8, diabetic rats with ERRα inhibition and performed ET. After 4 weeks, the animals were sacrificed and the liver was used for Real-Time PCR and Western blotting. Our results showed that ET significantly increased AMPK and SIRT1 gene and protein, and ERRα gene expression in healthy and diabetic rats compared to healthy and diabetic control groups. ERRα inhibition increased AMPK, SIRT1, SREBP-1c and ACC expression compared to control and ET groups. In healthy and diabetic rats, the combination of ERRα inhibition and ET significantly increased AMPK, SIRT1, SREBP-1c and ACC expression compared to healthy and diabetic control animals. Briefly, the combination of ET and ERRα disruption probably can be considered as a potential therapeutic intervention in diabetes but this hypothesis needs more evaluation to be cleared.