TY - JOUR

T1 - All-trans retinoic acid increases oxidative metabolism in mature adipocytes

AU - Mercader, Josep

AU - Madsen, Lise

AU - Felipe, Francisco

AU - Palou, Andreu

AU - Kristiansen, Karsten

AU - Bonet, M Luisa

N1 - Keywords: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Fatty Acids; Gene Expression Regulation; Ion Channels; Lipid Metabolism; Lipogenesis; Mice; Mitochondrial Proteins; Oxidation-Reduction; Phosphorylation; Retinoblastoma Protein; Transcription Factors; Tretinoin; Triglycerides; p38 Mitogen-Activated Protein Kinases

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 17975308

VL - 20

SP - 1061

EP - 1072

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

SN - 1015-8987

IS - 6

ER -