All-Trans Retinoic Acid Decreases Murine Adipose Retinol Binding Protein 4 Production

Vol. 22, No. 1-4, 2008

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Original Paper

All-Trans Retinoic Acid Decreases Murine Adipose Retinol Binding Protein 4 Production
Josep Mercader, Nuria Granados, Luisa Bonet, Andreu Palou

Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain, CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain

Address of Corresponding Author

Cell Physiol Biochem 2008;22:363-372 (DOI: 10.1159/000149815)

Key Words

Vitamin A
Retinoic acid
Retinaldehyde
Adipokines
Insulin resistance
Adipocyte

Abstract

Background/Aims: Adipose-derived retinol binding protein 4 (RBP4) might contribute to the development of insulin resistance, and therefore further knowledge of factors regulating it is of interest. Retinoic acid, the acid form of vitamin A, affects the expression of several adipokines related to insulin sensitivity in mice. Here, we sought to investigate its impact on adipose RBP4 production. Methods: Changes in RBP4 expression were analyzed in adipose tissues and liver of mice treated in vivo with all-trans retinoic acid (ATRA), and in 3T3-L1 adipocytes and adipocytes derived from mouse embryonic fibroblasts exposed to ATRA. Results: ATRA treatment in mice increased insulin sensitivity as assessed by the homeostatic model assessment for insulin resistance, and led to a reduction of RBP4 mRNA and protein levels in adipose tissues, a reduction of RBP4 protein but not RBP4 mRNA levels in the liver, and a marked increase in circulating RBP4 protein levels. In adipocyte cell models, ATRA down-regulated RBP4 mRNA levels in a dose-dependent manner: this effect was reproduced by retinaldehyde and retinoid receptors agonists, and correlated with a reduced accumulation of RBP4 protein in the culture medium. Conclusion: These results reveal a selective effect of ATRA inhibiting RBP4 expression specifically in adipocytes, and reinforce the concept that vitamin A vitamers may affect insulin sensitivity through effects on adipokine production.

Author Contacts

Dr. M. Luisa Bonet
Departament de Biologia Fonamental i Ciències de la Salut
Universitat de les Illes Balears
Crta. Valldemossa Km 7.5, 07122 Palma de Mallorca (Spain)
Tel. +34 971 172734, Fax: +34 971 173184, E-Mail luisabonet@uib.es

Article Information

Accepted: April 21, 2008
Published online: July 25, 2008
Number of Print Pages : 10

Medline Abstract (ID 18769064)

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