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

Obesity (Silver Spring). 2013 Jan;21(1):E22-5. doi: 10.1002/oby.20013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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