| Autor: |
Sébastien Vankoningsloo, Marie Piens, Christophe Lecocq, Audrey Gilson, Aurélia De Pauw, Patricia Renard, Catherine Demazy, Andrée Houbion, Martine Raes, Thierry Arnould |
| Jazyk: |
angličtina |
| Rok vydání: |
2005 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 46, Iss 6, Pp 1133-1149 (2005) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M400464-JLR200 |
| Popis: |
Mitochondrial cytopathy has been associated with modifications of lipid metabolism in various situations, such as the acquisition of an abnormal adipocyte phenotype observed in multiple symmetrical lipomatosis or triglyceride (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged red fibers syndrome. However, the molecular signaling leading to fat metabolism dysregulation in cells with impaired mitochondrial activity is still poorly understood. Here, we found that preadipocytes incubated with inhibitors of mitochondrial respiration such as antimycin A (AA) accumulate TG vesicles but do not acquire specific markers of adipocytes. Although the uptake of TG precursors is not stimulated in 3T3-L1 cells with impaired mitochondrial activity, we found a strong stimulation of glucose uptake in AA-treated cells mediated by calcium and phosphatidylinositol 3-kinase/Akt1/glycogen synthase kinase 3β, a pathway known to trigger the translocation of glucose transporter 4 to the plasma membrane in response to insulin. TG accumulation in AA-treated cells is mediated by a reduced peroxisome proliferator-activated receptor γ activity that downregulates muscle carnitine palmitoyl transferase-1 expression and fatty acid β-oxidation, and by a direct conversion of glucose into TGs accompanied by the activation of carbohydrate-responsive element binding protein, a lipogenic transcription factor.Taken together, these results could explain how mitochondrial impairment leads to the multivesicular phenotype found in some mitochondria-originating diseases associated with a dysfunction in fat metabolism. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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