Mild mitochondrial uncoupling induces 3T3-L1 adipocyte de-differentiation by a PPARγ-independent mechanism, whereas TNFα-induced de-differentiation is PPARγ dependent
Open accessAbstract
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.
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By acting on white adipocyte mass, mitochondrial uncouplers could protect against diabetes.
“By acting on white adipocyte mass, mitochondrial uncouplers could protect against diabetes, as limiting hyperaccumulation of triacyglycerol (TAG) in these cells might limit organelle stress [91,273,274,275] and modifications in the expression pattern of genes encoding adipokines, which are known to communicate the level of adiposity to other organs [221,276].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [273]
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References 73 · Cited by 46
- Authors
- Tejerina, S., De Pauw, A., Vankoningsloo, S., Houbion, A., Renard, P., De Longueville, F., Raes, M., & Arnould, T.
- Affiliations
- University of Namur (BE)
- Laboratory of Biochemistry and Cellular Biology, University of Namur (FUNDP), 61 Rue de Bruxelles, 5000 Namur, Belgium
- Eppendorf Array Technologies, 12 Rue du Séminaire, 5000 Namur, Belgium
- Corresponding author
- Arnould, Thierry
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2009-01-01
- Volume
- 122
- Issue
- 1
- Pages
- 145-155
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2032662185
- Cited by
- 46
- References
- 73
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 2 · 2014: 1 · 2013: 5 · 2012: 6
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- mitochondrial uncoupling, FCCP, PPARγ, C/EBPα, TNF-α, lipogenesis, lipolysis, perilipin A, 3T3-L1 adipocytes, obesity, rosiglitazone, 9-cis-retinoic acid
- MeSH terms
- Animals, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Mitochondria, Tumor Necrosis Factor-alpha, Uncoupling Agents, Biomarkers, Gene Expression Profiling, 3T3-L1 Cells, Retinoid X Receptors, PPAR gamma, Lipid Metabolism, Mice, Cell Dedifferentiation
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