MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Institute of Ecological Environment, Taizhou Academy of Agricultural Sciences, Taizhou, Zhejiang, China.
MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
J Nutr Biochem. 2022 Nov;109:109104. doi: 10.1016/j.jnutbio.2022.109104. Epub 2022 Jul 19.
Iron exerts significant influences on glucose metabolism. However, the regulatory mechanisms underlying disordered glucose response remains largely unclear. The aim of this study was to examine the impact of dietary iron on hepatic gluconeogenesis in mice and in rat liver-derived cells. High iron models of C57BL/6J mice were fed with 1.25 g Fe/kg diets for 9 weeks, and high-iron BRL-3A cell models were treated with 250 μmol/L FeSO for 12 h and 24 h. Our data showed that higher iron intake resulted in higher hepatic iron without iron toxicity, and reduced body weight gain with no difference of food intakes. High dietary iron significantly increased 61% of hepatic glycogen deposition, but exhibited impairment in glucose responses in mice. Moreover, high dietary iron suppressed hepatic gluconeogenesis by repressing the expression of key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, mice fed with higher iron diets exhibited both decreased AMP-activated protein kinase (AMPK) activity and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) protein levels. Furthermore, in BRL-3A cells, iron treatment increased cellular glucose uptake, and altered gluconeogenesis rhythmically by regulating the activation of AMPK and expression of PGC-1α successively. This study demonstrated that dietary high iron was able to increase hepatic glycogen deposition by enhancement of glucose uptake, and suppress hepatic gluconeogenesis by regulation of AMPK and PGC-1α.
铁对葡萄糖代谢有重要影响。然而，葡萄糖反应紊乱的调节机制仍很大程度上不清楚。本研究旨在研究膳食铁对小鼠肝糖异生和大鼠肝源性细胞的影响。采用 1.25 g Fe/kg 饮食喂养 C57BL/6J 小鼠 9 周，建立高铁模型；用 250 μmol/L FeSO4 处理大鼠肝源性细胞 BRL-3A 12 h 和 24 h，建立高铁模型。我们的数据表明，较高的铁摄入量导致肝脏铁含量升高而无铁毒性，体重增加减少而食物摄入量无差异。高膳食铁显著增加 61%的肝糖原沉积，但小鼠的葡萄糖反应受损。此外，高膳食铁通过抑制关键糖异生酶磷酸烯醇丙酮酸羧激酶和葡萄糖-6-磷酸酶的表达来抑制肝糖异生。同时，高铁饮食喂养的小鼠表现出 AMP 激活的蛋白激酶 (AMPK) 活性和过氧化物酶体增殖物激活受体 γ 共激活物 1α (PGC-1α) 蛋白水平降低。此外，在 BRL-3A 细胞中，铁处理通过调节 AMPK 的激活和 PGC-1α 的表达依次改变葡萄糖摄取和糖异生的节律。本研究表明，膳食高铁能够通过增强葡萄糖摄取来增加肝糖原沉积，并通过调节 AMPK 和 PGC-1α 来抑制肝糖异生。
