ArticleProceedings of the National Academy of Sciences of the United States of America2015
Maternal intestinal HIF-2α is necessary for sensing iron demands of lactation in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Uric Acid Induces Hepatocytes Ferroptosis Through HIF-2α/DMT1-Mediated Iron Overload.International journal of molecular sciences · 2026Article
- Mechanism and regulation of iron absorption throughout the life cycle.Journal of advanced research · 2025Review
- Effects of hypoxia stress on the milk synthesis in bovine mammary epithelial cells.Journal of animal science and biotechnology · 2025Article
- High-Altitude Hypoxia Induces Excessive Erythrocytosis in Mice via Upregulation of the IntestinalBiomedicines · 2023Article
- Tetramethylpyrazine nitrone activates hypoxia-inducible factor and regulates iron homeostasis to improve renal anemia.Frontiers in pharmacology · 2022Article
- Iron and manganese transport in mammalian systems.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis.Cell metabolism · 2020Article
- A genetic mouse model of severe iron deficiency anemia reveals tissue-specific transcriptional stress responses and cardiac remodeling.The Journal of biological chemistry · 2019Article
- Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload.The Journal of clinical investigation · 2019Article
- In silico mapping of quantitative trait loci (QTL) regulating the milk ionome in mice identifies a milk iron locus on chromosome 1.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Article
- Cyp1b1 deletion and retinol deficiency coordinately suppress mouse liver lipogenic genes and hepcidin expression during post-natal development.Molecular and cellular endocrinology · 2017Article
- Intestinal hephaestin potentiates iron absorption in weanling, adult, and pregnant mice under physiological conditions.Blood advances · 2017Article
- Epithelial Hypoxia-Inducible Factor 2α Facilitates the Progression of Colon Tumors through Recruiting Neutrophils.Molecular and cellular biology · 2017Article
- HIF2α Is an Essential Molecular Brake for Postprandial Hepatic Glucagon Response Independent of Insulin Signaling.Cell metabolism · 2016Article
- Myeloid Hif2α is not essential to maintain systemic iron homeostasis.Experimental hematologyArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The mechanisms that are essential for the maintenance of nutrient status in breast milk are unclear. Our data demonstrate that the intestine via hypoxia-inducible factor (HIF)-2α is an essential regulatory mechanism for maintaining the quality of breast milk. During lactation, intestinal HIF-2α is highly increased, leading to an adaptive induction of apical and basolateral iron transport genes. Disruption of intestinal HIF-2α (but not HIF-1α) or the downstream target gene divalent metal transporter (DMT)-1 in lactating mothers did not alter systemic iron homeostasis in the mothers, but led to anemia, decreased growth, and truncal alopecia in pups which was restored following weaning. Moreover, pups born from mothers with a disruption of intestinal HIF-2α led to long-term cognitive defects. Cross-fostering experiments and micronutrient profiling of breast milk demonstrated that the defects observed were due to decreased maternal iron delivery via milk. Increasing intestinal iron absorption by activation of HIF-2α or parenteral administration of iron-dextran in HIF-2α knockout mothers ameliorated anemia and restored neonatal development and adult cognitive functions. The present work details the importance of breast milk iron in neonatal development and uncovers an unexpected molecular mechanism for the regulation of nutritional status of breast milk through intestinal HIF-2α.
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