Induction of uncoupling protein-1 in mouse embryonic fibroblast-derived adipocytes by retinoic acid.
The uncoupling protein-1 (UCP1) is the molecular effector of thermogenesis in brown adipocytes, a process in which there is a renewed interest after the recent recognition of its relevance in adult humans. Typical white adipocytes do not express UCP1. We investigated the capacity of retinoic acid (RA), the carboxylic acid form of vitamin A and a known positive regulator of UCP1 gene transcription in brown adipocytes, to stimulate UCP1 expression in adipocytes differentiated in culture from primary mouse embryonic fibroblasts (MEFs), which are commonly used as white adipocyte model cells. Exposure to all-trans RA (ATRA), but not to rosiglitazone or isoproterenol, potently induced UCP1 expression at both the mRNA and protein level in MEF-derived adipocytes, in a dose-dependent manner. The effect on UCP1 mRNA was reproduced by retinoid receptor agonists and by retinaldehyde, required p38 mitogen-activated protein kinase activity (p38 MAPK), and appeared to be dissociated from increases in mitochondria biogenesis and oxidative capacity. MEF-derived adipocytes exhibited a high mRNA expression level of the brown fat determination factor PRDM16. The results highlight a specific potential of retinoids to induce UCP1 gene expression in adipose cells, and may have implications for the elucidation of the signaling pathways to the UCP1 gene, as well as for research using MEF-derived adipocytes.
Mercader
Josep
J
Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain.
Palou
Andreu
A
Bonet
M Luisa
ML
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012172:Retinaldehyde; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C416371:PRDM16 protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014212:Tretinoin; D048051:p38 Mitogen-Activated Protein Kinases; D012172:Retinaldehyde