Dietary iron modulates hepatic glucose homeostasis via regulating gluconeogenesis
Dietary iron modulates hepatic glucose homeostasis via regulating gluconeogenesis
复制标题
膳食铁通过调节糖异生来调节肝葡萄糖稳态
DOI：
10.1016/j.jnutbio.2022.109104
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发表时间：
2022
影响因子：
5.6
通讯作者：
Huahua Du
中科院分区：
文献类型：
--
作者：
Jiahui Li;Li Jia;Wan Ma;Yunfei Feng;Hong Yu;Huahua Du
铁对葡萄糖代谢有很大影响。然而，葡萄糖反应紊乱背后的调控机制在很大程度上仍不清楚。本研究的目的是研究膳食铁对小鼠和大鼠肝细胞糖异生的影响。高铁模型C57BL/6J小鼠以1.25gFe/kg饲喂9周，高铁BRL-3A细胞模型用2 5 0μ/L FeSO4处理12h和2 4h，结果表明，高铁摄入导致肝脏铁含量增加而无铁毒性，体重增加，但摄食量无差异。高铁饮食显著增加了小鼠肝脏糖原沉积的61%，但表现出葡萄糖反应的损害。此外，高铁通过抑制关键的糖异生酶、磷酸烯醇式丙酮酸羧激酶和葡萄糖-6-磷酸酶的表达，抑制了肝脏的糖异生。同时，喂食高铁饲料的小鼠表现出AMPK活性和过氧化体增殖物激活受体γ辅活化子1α(PGC-1α)蛋白水平的降低。此外，在BRL-3A细胞中，铁处理增加了细胞对葡萄糖的摄取，并通过调节AMPK的激活和PGC-1α的表达而节律性地改变了糖异生。本研究表明，高铁可通过促进葡萄糖摄取增加肝糖原沉积，并通过调节AMPK和PGC-1α抑制肝糖异生。
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 4 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.