Serum iron and transferrin saturation variation are circadian regulated and linked to the harmonic circadian oscillations of erythropoiesis and hepatic Tfrc expression in mice

Bennett, C; Pettikiriarachchi, A; McLean, ARD; Harding, R; Blewitt, ME; Seillet, C; Pasricha, SR

Author(s): Bennett, C; Pettikiriarachchi, A; McLean, ARD; Harding, R; Blewitt, ME; Seillet, C; Pasricha, SR;
Details: Publication Year 2024-08-17,Volume 99,Issue #11,Page 2075-2083
Journal Title: American Journal of Hematology
Abstract: Serum iron has long been thought to exhibit diurnal variation and is subsequently considered an unreliable biomarker of systemic iron status. Circadian regulation (endogenous ~24-h periodic oscillation of a biologic function) governs many critical physiologic processes. It is unknown whether serum iron levels are regulated by circadian machinery; likewise, the circadian nature of key players of iron homeostasis is unstudied. Here we show that serum iron, transferrin saturation (TSAT), hepatic transferrin receptor (TFR1) gene (Tfrc) expression, and erythropoietic activity exhibit circadian rhythms. Daily oscillations of serum iron, TSAT, hepatic Tfrc expression, and erythropoietic activity are maintained in mice housed in constant darkness, where oscillation reflects an endogenous circadian period. Oscillations of serum iron, TSAT, hepatic Tfrc, and erythropoietic activity were ablated when circadian machinery was disrupted in Bmal1 knockout mice. Interestingly, we find that circadian oscillations of erythropoietic activity and hepatic Tfrc expression are maintained in opposing phase, likely allowing for optimized usage and storage of serum iron whilst maintaining adequate serum levels and TSAT. This study provides the first confirmatory evidence that serum iron is circadian regulated, discerns circadian rhythms of TSAT, a widely used clinical marker of iron status, and uncovers liver-specific circadian regulation of TFR1, a major player in cellular iron uptake.
Publisher: Wiley
Keywords: Animals; *Receptors, Transferrin/genetics/blood; *Iron/metabolism/blood; *Erythropoiesis; *Liver/metabolism; Mice; *Circadian Rhythm; *Transferrin/metabolism; *Mice, Knockout; ARNTL Transcription Factors/genetics; Male; Mice, Inbred C57BL; Gene Expression Regulation
Research Division(s): Population Health And Immunity; Immunology
PubMed ID: 39152780
Publisher's Version: https://doi.org/10.1002/ajh.27447
Open Access at Publisher's Site: https://doi.org/ 10.1002/ajh.27447
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-23 02:54:10

Last Modified: 2024-10-25 10:50:49