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A retinoic acid receptor agonist tamibarotene suppresses iron accumulation in the liver
Authors:Osamu Yoshikawa  Yu Ebata  Hiroyuki Tsuchiya  Arisa Kawahara  Chihiro Kojima  Yoshito Ikeda  Susumu Hama  Kentaro Kogure  Koichi Shudo  Goshi Shiota
Institution:1. Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan;2. Research Foundation Itsuu Laboratory, Tokyo, Japan;3. Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan
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/β 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‐Ay 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.
Keywords:
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