Mild mitochondrial uncoupling induces 3T3-L1 adipocyte de-differentiation by a PPARγ-independent mechanism, whereas TNFα-induced de-differentiation is PPARγ dependent
| Autor: | Françoise de Longueville, Andrée Houbion, Thierry Arnould, Aurélia De Pauw, Silvia Tejerina, Patricia Renard, Martine Raes, Sébastien Vankoningsloo |
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| Přispěvatelé: | FUNDP - SBIO_URBC (unité de recherche en biologie cellulaire), UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/IREC - Institut de recherche expérimentale et clinique |
| Rok vydání: | 2009 |
| Předmět: |
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Cell Dedifferentiation - physiology medicine.medical_specialty Cellular differentiation Retinoic acid Mitochondrion Biology Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology Mice chemistry.chemical_compound Biological Markers - metabolism Downregulation and upregulation 3T3-L1 Cells Adipocyte Internal medicine medicine Animals Mitochondria - drug effects metabolism Beta oxidation Retinoid X Receptors - metabolism Tumor Necrosis Factor-alpha Uncoupling Agents Gene Expression Profiling 3T3-L1 Cells - metabolism Cell Biology Cell Dedifferentiation Lipid Metabolism Mitochondria PPAR gamma Retinoid X Receptors Endocrinology chemistry Adipogenesis Tumor Necrosis Factor-alpha - metabolism PPAR gamma - metabolism Uncoupling Agents - pharmacology Perilipin Biomarkers |
| Zdroj: | Journal of Cell Science, Vol. 122, no. 1, p. 145-55 (2009) |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.027508 |
| Popis: | Impairment of mitochondrial activity affects lipid-metabolizing tissues and mild mitochondrial uncoupling has been proposed as a possible strategy to fight obesity and associated diseases. In this report, we characterized the 3T3-L1-adipocyte ;de-differentiation' induced by carbonyl cyanide (p-trifluoromethoxy)-phenylhydrazone (FCCP), a mitochondrial uncoupler. We found a decrease in triglyceride (TG) content in adipocytes incubated with this molecule. We next analyzed the expression of genes encoding adipogenic markers and effectors and compared the differentially expressed genes in adipocytes treated with FCCP or TNFalpha (a cytokine known to induce adipocyte de-differentiation). Furthermore, a significant decrease in the transcriptional activity of PPARgamma and C/EBPalpha transcription factors was found in adipocytes with impaired mitochondrial activity. However, although these modifications were also found in TNFalpha-treated adipocytes, rosiglitazone and 9-cis retinoic acid (PPARgamma and RXR ligands) were unable to prevent triglyceride loss in FCCP-treated cells. Metabolic assays also revealed that TG reduction could be mediated by a downregulation of lipid synthesis rather than an upregulation of fatty acid oxidation. Finally, lipolysis stimulated by the uncoupler also seems to contribute to the TG reduction, a process associated with perilipin A downregulation. These results highlight some new mechanisms that might potentially be involved in adipocyte de-differentiation initiated by a mitochondrial uncoupling. |
| Databáze: | OpenAIRE |
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