Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice

Stela McLachlan, Kathryn E. Page, Seung-Min Lee, Alex Loguinov, Erika Valore, Simon T. Hui, Grace Jung, Jie Zhou, Aldons J. Lusis, Brie Fuqua, Tomas Ganz, Elizabeta Nemeth, Chris D. Vulpe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 (Hamp1) 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, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 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 Hamp1 mRNA levels in mice fed ironsufficient or high-iron diets, nor are the Hamp1 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 ironsufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY 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 Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males.

Original languageEnglish
Pages (from-to)G511-G523
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume313
Issue number5
DOIs
Publication statusPublished - 2017 Nov 2

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Hepcidins
Iron
Messenger RNA
Liver
Diet
RNA Sequence Analysis
Peptide Hormones

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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. / Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2017 ; Vol. 313, No. 5. pp. G511-G523.
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title = "Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice",
abstract = "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 (Hamp1) 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, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 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 Hamp1 mRNA levels in mice fed ironsufficient or high-iron diets, nor are the Hamp1 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 ironsufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY 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 Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males.",
author = "Stela McLachlan and Page, {Kathryn E.} and Seung-Min Lee and Alex Loguinov and Erika Valore and Hui, {Simon T.} and Grace Jung and Jie Zhou and Lusis, {Aldons J.} and Brie Fuqua and Tomas Ganz and Elizabeta Nemeth and Vulpe, {Chris D.}",
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McLachlan, S, Page, KE, Lee, S-M, Loguinov, A, Valore, E, Hui, ST, Jung, G, Zhou, J, Lusis, AJ, Fuqua, B, Ganz, T, Nemeth, E & Vulpe, CD 2017, 'Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 313, no. 5, pp. G511-G523. https://doi.org/10.1152/ajpgi.00307.2016

Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice. / 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.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 313, No. 5, 02.11.2017, p. G511-G523.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice

AU - McLachlan, Stela

AU - Page, Kathryn E.

AU - Lee, Seung-Min

AU - Loguinov, Alex

AU - Valore, Erika

AU - Hui, Simon T.

AU - Jung, Grace

AU - Zhou, Jie

AU - Lusis, Aldons J.

AU - Fuqua, Brie

AU - Ganz, Tomas

AU - Nemeth, Elizabeta

AU - Vulpe, Chris D.

PY - 2017/11/2

Y1 - 2017/11/2

N2 - 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 (Hamp1) 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, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 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 Hamp1 mRNA levels in mice fed ironsufficient or high-iron diets, nor are the Hamp1 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 ironsufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY 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 Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males.

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