The Importance of Transfer Receptor 1 in Adipose Tissue

Abstract

Iron homeostasis is essential for maintaining cellular function in a variety of cell types. Transferrin receptor 1 (TfR1), which is expressed ubiquitously, facilitates cellular iron (Fe) uptake through receptor-mediated endocytosis of Fe-loaded transferrin. This study was undertaken to evaluate the importance of TfR1-mediated Fe import into adipose tissues for thermogenesis and systemic metabolism. We found that adipose-specific TfR1 knockout mice exhibited severe cold susceptibility upon acute cold exposure, leading to death of the mutant mice within hours. This phenotype was exacerbated by dietary Fe limitation and partially rescued by Fe administration. Knockout mice showed marked defects in oxidative phosphorylation components and lipid droplet homeostasis in adipose tissues. Furthermore, elevated levels of plasma glucose and insulin in the mutant’s hint at an unexpected connection between adipocyte Fe deficiency and diabetes. Altogether, our results suggest that TfR1-mediated Fe uptake is critical for multiple aspects of adipose function and systemic energy metabolism.