title: All-trans retinoic acid increases oxidative metabolism in mature adipocytes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The results indicate that RA directly favors remodeling of mature 3T3-L1 adipocytes in culture toward increased oxidative metabolism.
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illws Balears, Palma de Mallorca, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Mercader
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.forename: Francisco
authors.initials: F
authors.lastname: Felipe
authors.forename: Andreu
authors.initials: A
authors.lastname: Palou
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Bonet
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014212:Tretinoin; D048051:p38 Mitogen-Activated Protein Kinases