Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle.
Publication/Presentation Date
11-1-2015
Abstract
Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non-hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that iron assimilation via Tfr1 was critical for skeletal muscle metabolism, and that iron deficiency in muscle led to dramatic changes, not only in muscle, but also in adipose tissue and liver. Inactivation of Tfr1 incapacitated normal energy production in muscle, leading to growth arrest and a muted attempt to switch to fatty acid β oxidation, using up fat stores. Starvation signals stimulated gluconeogenesis in the liver, but amino acid substrates became limiting and hypoglycemia ensued. Surprisingly, the liver was also iron deficient, and production of the iron regulatory hormone hepcidin was depressed. Our observations reveal a complex interaction between iron homeostasis and metabolism that has implications for metabolic and iron disorders.
Volume
2
Issue
11
First Page
1705
Last Page
1717
ISSN
2352-3964
Published In/Presented At
Barrientos, T., Laothamatas, I., Koves, T. R., Soderblom, E. J., Bryan, M., Moseley, M. A., Muoio, D. M., & Andrews, N. C. (2015). Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle. EBioMedicine, 2(11), 1705–1717. https://doi.org/10.1016/j.ebiom.2015.09.041
Disciplines
Medicine and Health Sciences
PubMedID
26870796
Department(s)
Fellows and Residents
Document Type
Article