McLachlan Stela, Page Kathryn E, Lee Seung-Min, Loguinov Alex, Valore Erika, Hui Simon T, Jung Grace, Zhou Jie, Lusis Aldons J, Fuqua Brie, Ganz Tomas, Nemeth Elizabeta, Vulpe Chris D
Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom;
Department of Nutritional Science & Toxicology, University of California, Berkeley, California.
Am J Physiol Gastrointest Liver Physiol. 2017 Nov 1;313(5):G511-G523. doi: 10.1152/ajpgi.00307.2016. Epub 2017 Aug 10.
Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin () mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of mRNA levels in mice, nor are the mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males.
铁稳态受到严格调控，肽激素铁调素被认为是铁代谢的主要调节因子。先前在少数小鼠品系中进行的研究发现，铁调素的mRNA和血清水平存在不明确的性别和品系依赖性差异，并且关于铁调素（）mRNA水平与铁状态之间的关系报道的数据相互矛盾。我们的目的是通过检查多个组织以及不同饮食条件对多个近交系的影响，来阐明品系、性别和铁调素表达之间的关系。进行了两项研究：首先，在14个近交系中测量了对照饮食下的mRNA、肝脏铁和血浆双铁转铁蛋白水平；其次，在铁充足或高铁饮食饲养的9个近交/重组近交系中，测量了雄性和雌性的mRNA和血浆铁调素水平以及雄性心脏、肾脏、肝脏、胰腺和脾脏中的铁水平。性别和品系对铁调素mRNA（主要是性别效应）和血浆铁调素水平（主要是品系效应）均有显著影响。然而，对于喂食铁充足或高铁饮食的小鼠，肝脏铁和双铁转铁蛋白水平不是mRNA水平的预测指标，至少在雄性中，mRNA和血浆铁调素水平也不是组织铁水平的良好预测指标。我们还测量了血浆红细胞铁调素，对喂食铁充足、低铁或高铁饮食的6个近交系的肝脏样本进行了RNA测序分析，并探讨了铁调素水平最高和最低的品系之间的基因表达差异。性别和品系对铁调素mRNA（主要是性别效应）和血浆铁调素水平（主要是品系效应）均有显著影响。肝脏铁和双铁转铁蛋白水平不是小鼠mRNA水平的预测指标，至少在雄性中，mRNA和血浆铁调素水平也不是组织铁水平的良好预测指标。
