Tourniaire Franck, Musinovic Hana, Gouranton Erwan, Astier Julien, Marcotorchino Julie, Arreguin Andrea, Bernot Denis, Palou Andreu, Bonet M Luisa, Ribot Joan, Landrier Jean-François
INRA, UMR 1260, F-13385, Marseille, France INSERM, UMR 1062, "Nutrition, Obésité et Risque Thrombotique," F-13385, Marseille, France Aix-Marseille Université, Faculté de Médecine, F-13385, Marseille, France.
Laboratory of Molecular Biology, Nutrition and Biotechnology/Nutrigenomics-group, Universitat de les Illes Balears, and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain.
J Lipid Res. 2015 Jun;56(6):1100-9. doi: 10.1194/jlr.M053652. Epub 2015 Apr 25.
A positive effect of all-trans retinoic acid (ATRA) on white adipose tissue (WAT) oxidative and thermogenic capacity has been described and linked to an in vivo fat-lowering effect of ATRA in mice. However, little is known about the effects of ATRA on mitochondria in white fat. Our objective has been to characterize the effect of ATRA on mitochondria biogenesis and oxidative phosphorylation (OXPHOS) capacity in mature white adipocytes. Transcriptome analysis, oxygraphy, analysis of mitochondrial DNA (mtDNA), and flow cytometry-based analysis of mitochondria density were performed in mature 3T3-L1 adipocytes after 24 h incubation with ATRA (2 µM) or vehicle. Selected genes linked to mitochondria biogenesis and function and mitochondria immunostaining were analyzed in WAT tissues of ATRA-treated as compared with vehicle-treated mice. ATRA upregulated the expression of a large set of genes linked to mtDNA replication and transcription, mitochondrial biogenesis, and OXPHOS in adipocytes, as indicated by transcriptome analysis. Oxygen consumption rate, mtDNA content, and staining of mitochondria were increased in the ATRA-treated adipocytes. Similar results were obtained in WAT depots of ATRA-treated mice. We conclude that ATRA impacts mitochondria in adipocytes, leading to increased OXPHOS capacity and mitochondrial content in these cells.
全反式维甲酸（ATRA）对白色脂肪组织（WAT）的氧化和产热能力具有积极作用，这一作用已被描述，且与ATRA在小鼠体内的降脂作用有关。然而，关于ATRA对白色脂肪中线粒体的影响，人们知之甚少。我们的目标是表征ATRA对成熟白色脂肪细胞中线粒体生物发生和氧化磷酸化（OXPHOS）能力的影响。在用ATRA（2 μM）或溶剂处理24小时后，对成熟的3T3-L1脂肪细胞进行转录组分析、氧电极法分析、线粒体DNA（mtDNA）分析以及基于流式细胞术的线粒体密度分析。与溶剂处理的小鼠相比，对经ATRA处理的小鼠的WAT组织进行分析，测定与线粒体生物发生和功能相关的选定基因以及线粒体免疫染色情况。转录组分析表明，ATRA上调了大量与脂肪细胞中mtDNA复制和转录、线粒体生物发生以及OXPHOS相关的基因的表达。经ATRA处理的脂肪细胞中的耗氧率、mtDNA含量以及线粒体染色均增加。在经ATRA处理的小鼠的WAT库中也获得了类似结果。我们得出结论，ATRA影响脂肪细胞中的线粒体，导致这些细胞中OXPHOS能力和线粒体含量增加。
