Laboratory of Bioenvironmental Sciences, Course of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku Ohrai-Kita, Izumisano, Osaka, 598-8531, Japan.
Laboratory of Bioenvironmental Sciences, Course of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku Ohrai-Kita, Izumisano, Osaka, 598-8531, Japan.
Arch Biochem Biophys. 2021 Sep 15;708:108960. doi: 10.1016/j.abb.2021.108960. Epub 2021 Jun 5.
In erythropoietin (EPO)-producing HepG2 cells, we investigated the effect of trivalent chromium (Cr) on the promotion of EPO production and the induction of insulin resistance. Cr increased hypoxia-inducible factor (HIF)-1α protein, EPO mRNA expression and EPO protein levels in HepG2 cells. The effect of Cr on EPO production was inhibited by inhibition of proliferator-activated receptor γ (PPARγ). Insulin resistance was induced by culturing with insulin resistance induction medium supplemented with palmitic acid for 24 h. When Cr was added to the medium, the increase in glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 mRNA expression levels and the decrease in the ratio of phosphorylated Akt to Akt protein were suppressed, and the induction of insulin resistance prevented. When a PPARγ inhibitor or siPPARγ was added together with Cr, the inhibitory effect of Cr on the induction of insulin resistance disappeared. In addition, pretreatment with siEPO suppressed the increase in EPO mRNA expression, and the inhibitory effect on the induction of insulin resistance due to the addition of Cr was significantly reduced. These results suggest that the inhibition of insulin resistance induction by Cr in HepG2 cells involves the promotion of EPO production mediated by PPARγ, in addition to other PPARγ-mediated activities.
在产生红细胞生成素 (EPO) 的 HepG2 细胞中，我们研究了三价铬 (Cr) 对促进 EPO 产生和诱导胰岛素抵抗的影响。Cr 增加了 HepG2 细胞中缺氧诱导因子 (HIF)-1α 蛋白、EPO mRNA 表达和 EPO 蛋白水平。PPARγ 抑制剂抑制了 Cr 对 EPO 产生的影响。用含棕榈酸的胰岛素抵抗诱导培养基培养 24 小时可诱导胰岛素抵抗。当 Cr 添加到培养基中时，葡萄糖-6-磷酸酶和磷酸烯醇丙酮酸羧激酶 1 mRNA 表达水平的增加以及磷酸化 Akt 与 Akt 蛋白比值的降低受到抑制，从而阻止了胰岛素抵抗的诱导。当与 Cr 一起添加 PPARγ 抑制剂或 siPPARγ 时，Cr 对诱导胰岛素抵抗的抑制作用消失。此外，用 siEPO 预处理可抑制 EPO mRNA 表达的增加，并且由于添加 Cr 而导致的对胰岛素抵抗诱导的抑制作用显著降低。这些结果表明，Cr 抑制 HepG2 细胞中胰岛素抵抗的诱导除了涉及其他 PPARγ 介导的活性外，还涉及由 PPARγ 介导的 EPO 产生的促进作用。
