Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Barrientos, T; Laothamatas, I; Koves, TR; Soderblom, EJ; Bryan, M; Moseley, MA; Muoio, DM; Andrews, NC

Published Date

  • November 2015

Published In

Volume / Issue

  • 2 / 11

Start / End Page

  • 1705 - 1717

PubMed ID

  • 26870796

Pubmed Central ID

  • PMC4740293

Electronic International Standard Serial Number (EISSN)

  • 2352-3964

Digital Object Identifier (DOI)

  • 10.1016/j.ebiom.2015.09.041


  • eng

Conference Location

  • Netherlands