Hepatic Peroxisome Proliferator-Activated Receptor γ Coactivator 1α and Hepcidin Are Coregulated in Fasted/Refed States in Mice

To the Editor:Hepcidin plays a central role in iron homeostasis and contributes to the pathogenesis of several disorders. Consequently, development of a clear understanding of hepcidin regulation in various pathophysiological conditions has been the subject of intensive research. Technical limitations, however, have limited the wide availability of assays for measuring this iron-regulatory hormone in human serum. Recently, Troutt et al. developed a specific and robust sandwich immunoassay for hepcidin-25 and measured it in the serum of healthy volunteers. They reported diurnal variation in its concentrations in the circulation (1). In particular, the authors demonstrated that hepcidin-25 concentrations were significantly increased after 3 days of fasting, an intriguing result considering the hyposideremic effect of hepcidin. The authors hypothesized that this increase in hepcidin could be caused by suppressed erythropoiesis to maintain tissue iron concentrations.To investigate the molecular mechanisms responsible for hepcidin regulation by fasting, we fasted C57BL/6J mice for 24 h and then separated them into 2 groups. The first group was fasted for an additional 12-h period (“fasted” conditions); the second …