A retinoic acid receptor agonist tamibarotene suppresses iron accumulation in the liver.

ABSTRACT

OBJECTIVE: Hepatic iron overload (HIO) and iron-induced oxidative stress have recently emerged as an important factor for the development and progression of insulin resistance. The aim of this study was to evaluate the effect of tamibarotene, a selective retinoic acid receptor α/ß agonist, on hepatic iron metabolism, based on our previous findings that retinoids suppress hepatic iron accumulation by increasing hepatic iron efflux through the regulation of hemojuvelin and ferroportin expression. DESIGN AND METHODS: We quantitated the non-heme iron content and iron metabolism-related gene expression in the liver, and serum lipid and blood glucose levels in KK-A(y) mice after dietary administration of tamibarotene. RESULTS: It was demonstrated that tamibarotene significantly reduced blood glucose and hepatic iron, but not serum lipids, and that hemojuvelin expression significantly decreased while ferroportin increased, as observed previously. CONCLUSIONS: These results suggest that tamibarotene is a promising alternative for the treatment of insulin resistance associated with HIO.