High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism

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 ges...

Full description

Bibliographic Details
Main Authors: Minju Kim, Yeon-hee Kim, Sohyun Min, Seung-Min Lee
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/12/2451
_version_ 1797483666198233088
author Minju Kim
Yeon-hee Kim
Sohyun Min
Seung-Min Lee
author_facet Minju Kim
Yeon-hee Kim
Sohyun Min
Seung-Min Lee
author_sort Minju Kim
collection DOAJ
description 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<sub>4</sub> 0 g/1 kg) or high iron (HFe, FeSO<sub>4</sub> 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.
first_indexed 2024-03-09T22:50:17Z
format Article
id doaj.art-58ada3b71a624b18aeb93f6cf175eb88
institution Directory Open Access Journal
issn 2072-6643
language English
last_indexed 2024-03-09T22:50:17Z
publishDate 2022-06-01
publisher MDPI AG
record_format Article
series Nutrients
spelling doaj.art-58ada3b71a624b18aeb93f6cf175eb882023-11-23T18:21:20ZengMDPI AGNutrients2072-66432022-06-011412245110.3390/nu14122451High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid MetabolismMinju Kim0Yeon-hee Kim1Sohyun Min2Seung-Min Lee3Department of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, KoreaDepartment of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, KoreaDepartment of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, KoreaDepartment of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, KoreaIron 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<sub>4</sub> 0 g/1 kg) or high iron (HFe, FeSO<sub>4</sub> 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.https://www.mdpi.com/2072-6643/14/12/2451high dietary irondietary iron intakehigh iron exposurematernal iron statusferritin heavy chainiron homeostasis
spellingShingle Minju Kim
Yeon-hee Kim
Sohyun Min
Seung-Min Lee
High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
Nutrients
high dietary iron
dietary iron intake
high iron exposure
maternal iron status
ferritin heavy chain
iron homeostasis
title High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
title_full High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
title_fullStr High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
title_full_unstemmed High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
title_short High Iron Exposure from the Fetal Stage to Adulthood in Mice Alters Lipid Metabolism
title_sort high iron exposure from the fetal stage to adulthood in mice alters lipid metabolism
topic high dietary iron
dietary iron intake
high iron exposure
maternal iron status
ferritin heavy chain
iron homeostasis
url https://www.mdpi.com/2072-6643/14/12/2451
work_keys_str_mv AT minjukim highironexposurefromthefetalstagetoadulthoodinmicealterslipidmetabolism
AT yeonheekim highironexposurefromthefetalstagetoadulthoodinmicealterslipidmetabolism
AT sohyunmin highironexposurefromthefetalstagetoadulthoodinmicealterslipidmetabolism
AT seungminlee highironexposurefromthefetalstagetoadulthoodinmicealterslipidmetabolism