Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle

EBioMedicine

Indira Laothamatas¹  Deborah M. Muoio¹  Tomasa Barrientos¹  Nancy C. Andrews¹  Miles Bryan¹  Erik J. Soderblom²  M. Arthur Moseley²  Timothy R. Koves³ 

[1] Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA;Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University School of Medicine, Durham, NC 27710, USA;Molecular Physiology Institute, Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27704, USA;

关键词: Iron;    Skeletal muscle;    Transferrin receptor;    Hepcidin;    Intermediary metabolism;   

DOI  :  10.1016/j.ebiom.2015.09.041

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown