Department of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea.
Nutrients. 2022 Jun 13;14(12):2451. doi: 10.3390/nu14122451.
Iron supplementation is recommended during pregnancy and fetal growth. However, excess iron exposure may increase the risk of abnormal fetal development. We investigated the potential side effects of high iron levels in fetuses and through their adult life. C57BL/6J pregnant mice from 2 weeks of gestation and their offspring until 30 weeks were fed a control (CTRL, FeSO 0 g/1 kg) or high iron (HFe, FeSO 9.9 g/1 kg) diets. HFe group showed higher iron accumulation in the liver with increased hepcidin, reduced TfR1/2 mRNAs, and lowered ferritin heavy chain (FTH) proteins in both liver and adipose tissues despite iron loading. HFe decreased body weight, fat weight, adipocyte size, and triglyceride levels in the blood and fat, along with downregulation of lipogenesis genes, including PPARγ, C/EBPα, SREBP1c, FASN, and SCD1, and fatty acid uptake and oxidation genes, such as CD36 and PPARα. UCP2, adiponectin, and mRNA levels of antioxidant genes such as GPX4, HO-1, and NQO1 were increased in the HFe group, while total glutathione was reduced. We conclude that prolonged exposure to high iron from the fetal stage to adulthood may decrease fat accumulation by altering ferritin expression, adipocyte differentiation, and triglyceride metabolism, resulting in an alteration in normal growth.
孕期和胎儿生长期间推荐补充铁元素。然而，过量的铁暴露可能会增加胎儿发育异常的风险。我们研究了胎儿和成年期高铁水平的潜在副作用。从妊娠第 2 周开始，给 C57BL/6J 孕鼠及其后代喂食对照（CTRL，FeSO4 0 g/1 kg）或高铁（HFe，FeSO4 9.9 g/1 kg）饮食，直至 30 周。尽管铁负荷增加，但 HFe 组肝脏中铁的积累增加，铁调素升高，TfR1/2 mRNA 减少，肝脏和脂肪组织中的铁蛋白重链（FTH）蛋白降低。HFe 降低了体重、脂肪重量、脂肪细胞大小和血液及脂肪中的甘油三酯水平，并下调了脂肪生成基因，包括 PPARγ、C/EBPα、SREBP1c、FASN 和 SCD1，以及脂肪酸摄取和氧化基因，如 CD36 和 PPARα。UCP2、脂联素和抗氧化基因如 GPX4、HO-1 和 NQO1 的 mRNA 水平在 HFe 组中增加，而总谷胱甘肽减少。我们得出结论，从胎儿期到成年期持续暴露于高铁可能通过改变铁蛋白表达、脂肪细胞分化和甘油三酯代谢来减少脂肪积累，从而导致正常生长的改变。
