All-trans retinoic acid induces oxidative phosphorylation and mitochondria biogenesis in adipocytes.
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.
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.
Franck
F
Tourniaire
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.
Hana
H
Musinovic
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.
Erwan
E
Gouranton
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.
Julien
J
Astier
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.
Julie
J
Marcotorchino
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.
Andrea
A
Arreguin
Assistance Publique - Hôpitaux de Marseille, CHU La Timone, F-13385, Marseille, France.
Denis
D
Bernot
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.
Andreu
A
Palou
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.
M Luisa
ML
Bonet
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.
Joan
J
Ribot
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.
Jean-François
JF
Landrier
D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000378:metabolism; D001678:Organelle Biogenesis; D010085:Oxidative Phosphorylation; D014212:Tretinoin / Q000378:metabolism*
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D014212:Tretinoin
adipose tissue; browning; vitamin A