Mild mitochondrial uncoupling induces 3T3-L1 adipocyte de-differentiation by a PPARγ-independent mechanism, whereas TNFα-induced de-differentiation is PPARγ dependent
Copyright policy )Mild mitochondrial uncoupling induces 3T3-L1 adipocyte de-differentiation by a PPARγ-independent mechanism, whereas TNFα-induced de-differentiation is PPARγ dependent
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 TNFα (a cytokine known to induce adipocyte de-differentiation). Furthermore, a significant decrease in the transcriptional activity of PPARγ and C/EBPα transcription factors was found in adipocytes with impaired mitochondrial activity. However, although these modifications were also found in TNFα-treated adipocytes, rosiglitazone and 9-cis retinoic acid (PPARγ 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.
- Université Catholique de Louvain Belgium
- Université de Namur Belgium
- University of Namur Belgium
Cell Dedifferentiation - physiology, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology, Mice, Biological Markers - metabolism, 3T3-L1 Cells, Animals, Mitochondria - drug effects, metabolism, Retinoid X Receptors - metabolism, Tumor Necrosis Factor-alpha, Uncoupling Agents, Gene Expression Profiling, 3T3-L1 Cells - metabolism, Cell Dedifferentiation, Lipid Metabolism, Adipocyte de-diffenciation, Mitochondria, PPAR gamma, Retinoid X Receptors, Tumor Necrosis Factor-alpha - metabolism, PPAR gamma - metabolism, Uncoupling Agents - pharmacology, Gene expression, Mitochondrial dysfunction, Biomarkers
Cell Dedifferentiation - physiology, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology, Mice, Biological Markers - metabolism, 3T3-L1 Cells, Animals, Mitochondria - drug effects, metabolism, Retinoid X Receptors - metabolism, Tumor Necrosis Factor-alpha, Uncoupling Agents, Gene Expression Profiling, 3T3-L1 Cells - metabolism, Cell Dedifferentiation, Lipid Metabolism, Adipocyte de-diffenciation, Mitochondria, PPAR gamma, Retinoid X Receptors, Tumor Necrosis Factor-alpha - metabolism, PPAR gamma - metabolism, Uncoupling Agents - pharmacology, Gene expression, Mitochondrial dysfunction, Biomarkers
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).41 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!