Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Erythropoietin (EPO) has been reported to have various effects other than promoting hematopoiesis, including inhibition of insulin resistance induction. In a previous study, we reported that trivalent chromium (Cr) promotes EPO production and inhibits the insulin resistance induction in HepG2 cells. The action of Cr was thought to be mediated by PPARγ, but the relationship between EPO production and the insulin resistance induction is not clear. Therefore, we investigated the regulation of EPO production by Cr in HepG2 cells and the effect of the produced EPO on PPARγ. The addition of Cr increased the amount of PPARγ and HIF-1α protein, and EPO production. The addition of HIF-1α inhibitor suppressed the increase in PPARγ by Cr. The addition of Cr promoted the activation of Akt, but the addition of the Akt inhibitor suppressed the increase of HIF-1α and PPARγ due to Cr. Pretreatment with siEPO or siEPOR suppressed the increase in HIF-1α and PPARγ by Cr. Changes in the mRNA levels of Glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 and the ratio of phosphorylated Akt to Akt protein due to the addition of insulin, as index of insulin resistance, indicated that the insulin resistance induction was inhibited by Cr. Inhibition of HIF-1α or PPARγ suppressed the effect of Cr on insulin resistance. These results suggested that Cr not only increases PPARγ directly, but also increases PPARγ by increasing HIF-1α via Akt in HepG2 cells. In addition, EPO produced in HepG2 cells by Cr was considered to affect PPARγ via EPOR and to prevent the insulin resistance induction.
