All-Trans Retinoic Acid Increases Oxidative Metabolism in Mature Adipocytes

Vol. 20, No. 6, 2007

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Original Paper

All-Trans Retinoic Acid Increases Oxidative Metabolism in Mature Adipocytes
J. Mercader; L. Madsen; F. Felipe; A. Palou; K. Kristiansen; L. Bonet

^aLaboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca and CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, ^bDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense

Cell Physiol Biochem 2007;20:1061-1072
(DOI: 10.1159/000110717)

Summary

Background/Aims: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. Methods: Parameters of lipid metabolism and related gene expression were analyzed in differentiated 3T3-L1 adipocytes after exposure to RA or vehicle. Results: Treatment with RA resulted in decreased cellular triacylglycerol content and increased basal lipolysis and fatty acid oxidation rate. At the mRNA level, RA treatment led to a reduced expression of adipogenic/lipogenic transcription factors (peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, rexinoid receptor alpha) and two purported suppressors of lipolysis and oxidative metabolism (CIDEA and receptor-interacting protein 140), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were preceded by an early RA-induced phosphorylation of p38 mitogen-activated protein kinase. UCP1 expression was not induced. Conclusion: The results indicate that RA directly favors remodeling of mature 3T3-L1 adipocytes in culture toward increased oxidative metabolism.

Medline Abstract (ID 17975308)

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