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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Anderson, Erik R. Shah, Yatrik M. Ramakrishnan, Sadeesh K. Martin, Angelical Centofanti, Brook |
| Description | Author Affiliation: Ramakrishnan SK ( Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109); Anderson ER ( Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109); Martin A ( Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109); Centofanti B ( Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109); Shah YM ( Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109); |
| 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)-2 is an essential regulatory mechanism for maintaining the quality of breast milk. During lactation, intestinal HIF-2 is highly increased, leading to an adaptive induction of apical and basolateral iron transport genes. Disruption of intestinal HIF-2 (but not HIF-1 ) 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-2 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-2 or parenteral administration of iron-dextran in HIF-2 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-2 . |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 28 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Basic Helix-Loop-Helix Transcription Factors Physiology Intestines Metabolism Lactation Anemia Etiology Animals Animals, Newborn Cation Transport Proteins Homeostasis Mice Mice, Knockout Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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