Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle

Tomasa Barrientos, Indira Laothamatas, Timothy R. Koves, Erik J. Soderblom, Miles Bryan, M. Arthur Moseley, Deborah M. Muoio, Nancy C. Andrews

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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.

Original languageEnglish
Pages (from-to)1705-1717
Number of pages13
Issue number11
StatePublished - 1 Nov 2015
Externally publishedYes


  • Hepcidin
  • Intermediary metabolism
  • Iron
  • Skeletal muscle
  • Transferrin receptor


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