Dynamic Regulation of Genes Involved in Mitochondrial DNA Replication and Transcription during Mouse Brown Fat Cell Differentiation and Recruitment
| العنوان: | Dynamic Regulation of Genes Involved in Mitochondrial DNA Replication and Transcription during Mouse Brown Fat Cell Differentiation and Recruitment |
|---|---|
| المؤلفون: | Karen Dixen, Maria Murholm, Bjørn Quistorff, Lillian H. L. Hansen, Ez-Zoubir Amri, Giorgio Barbatelli, Klaus Qvortrup, Lise Madsen, Jacob B. Hansen |
| المساهمون: | Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Dept. Biochemistry and Molecular Biology, Odense, University of Southern Denmark (SDU) |
| المصدر: | PLoS ONE PLoS ONE, Public Library of Science, 2009, 4 (12), pp.e8458. ⟨10.1371/journal.pone.0008458⟩ PLoS ONE, Vol 4, Iss 12, p e8458 (2009) |
| بيانات النشر: | Public Library of Science, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Transcription, Genetic, MESH: Cold Temperature, Brown fat cell differentiation, Adipocytes, White, Gene Dosage, Adipose tissue, lcsh:Medicine, MESH: DNA Replication, MESH: Gene Dosage, Diabetes and Endocrinology/Obesity, Mice, 0302 clinical medicine, Cell Movement, Brown adipose tissue, MESH: Nuclear Receptor Co-Repressor 1, MESH: Animals, lcsh:Science, MESH: Cell Movement, [SDV.BDD]Life Sciences [q-bio]/Development Biology, PRDM16, MESH: Adipocytes, Brown, 0303 health sciences, Multidisciplinary, MESH: DNA, High Mobility Group Proteins, Cell Differentiation, MESH: Transcription Factors, MESH: Gene Expression Regulation, Thermogenin, Mitochondria, Cold Temperature, DNA-Binding Proteins, medicine.anatomical_structure, Adipocytes, Brown, 030220 oncology & carcinogenesis, Gene Knockdown Techniques, Mitochondrial DNA replication, Research Article, Protein Binding, MESH: Cell Differentiation, MESH: Cell Nucleus, DNA Replication, MESH: Mitochondria, MESH: Trans-Activators, Cell Biology/Developmental Molecular Mechanisms, Biology, DNA, Mitochondrial, 03 medical and health sciences, MESH: Mice, Inbred C57BL, medicine, MESH: Protein Binding, Animals, Nuclear Receptor Co-Repressor 1, MESH: Mice, Molecular Biology, Cell Biology/Gene Expression, 030304 developmental biology, Cell Nucleus, MESH: Transcription, Genetic, lcsh:R, MESH: DNA, Mitochondrial, DNA, TFAM, MESH: High Mobility Group Proteins, Molecular biology, MESH: Gene Knockdown Techniques, MESH: Adipocytes, White, Mice, Inbred C57BL, Mitochondrial biogenesis, Gene Expression Regulation, Developmental Biology/Cell Differentiation, Trans-Activators, lcsh:Q, Cell Biology/Morphogenesis and Cell Biology, MESH: DNA-Binding Proteins, Transcription Factors |
| الوصف: | International audience; BACKGROUND: Brown adipocytes are specialised in dissipating energy through adaptive thermogenesis, whereas white adipocytes are specialised in energy storage. These essentially opposite functions are possible for two reasons relating to mitochondria, namely expression of uncoupling protein 1 (UCP1) and a remarkably higher mitochondrial abundance in brown adipocytes. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a comprehensive characterisation of gene expression linked to mitochondrial DNA replication, transcription and function during white and brown fat cell differentiation in vitro as well as in white and brown fat, brown adipose tissue fractions and in selected adipose tissues during cold exposure. We find a massive induction of the majority of such genes during brown adipocyte differentiation and recruitment, e.g. of the mitochondrial transcription factors A (Tfam) and B2 (Tfb2m), whereas only a subset of the same genes were induced during white adipose conversion. In addition, PR domain containing 16 (PRDM16) was found to be expressed at substantially higher levels in brown compared to white pre-adipocytes and adipocytes. We demonstrate that forced expression of Tfam but not Tfb2m in brown adipocyte precursor cells promotes mitochondrial DNA replication, and that silencing of PRDM16 expression during brown fat cell differentiation blunts mitochondrial biogenesis and expression of brown fat cell markers. CONCLUSIONS/SIGNIFICANCE: Using both in vitro and in vivo model systems of white and brown fat cell differentiation, we report a detailed characterisation of gene expression linked to mitochondrial biogenesis and function. We find significant differences in differentiating white and brown adipocytes, which might explain the notable increase in mitochondrial content observed during brown adipose conversion. In addition, our data support a key role of PRDM16 in triggering brown adipocyte differentiation, including mitochondrial biogenesis and expression of UCP1. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2ce40ac09f4a8c48c2a0ba605060d33Test http://europepmc.org/articles/PMC2809086Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a2ce40ac09f4a8c48c2a0ba605060d33 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|