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/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-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.

• Authors: Osamu Yoshikawa, Yu Ebata, Hiroyuki Tsuchiya, Arisa Kawahara, Chihiro Kojima, Yoshito Ikeda, Susumu Hama, Kentaro Kogure, Koichi Shudo, Goshi Shiota
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 21 Issue 1 Pg. E22-5 (Jan 2013) ISSN: 1930-739X [Electronic] United States
• PMID: 23404745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 The Obesity Society.

Chemical References

• Benzoates
• Blood Glucose
• Cation Transport Proteins
• Lipids
• Rara protein, mouse
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• Tetrahydronaphthalenes
• metal transporting protein 1
• retinoic acid receptor beta
• tamibarotene
• Heme
• Iron

Topics

• Animals
• Benzoates (pharmacology, therapeutic use)
• Biological Transport
• Blood Glucose (metabolism)
• Cation Transport Proteins (metabolism)
• Gene Expression
• Heme (metabolism)
• Hemochromatosis (metabolism, prevention & control)
• Insulin Resistance
• Iron (metabolism)
• Iron Overload (metabolism, prevention & control)
• Lipids (blood)
• Liver (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred Strains
• Oxidative Stress
• Receptors, Retinoic Acid (agonists)
• Retinoic Acid Receptor alpha
• Tetrahydronaphthalenes (pharmacology, therapeutic use)