N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes
Oxidative stress plays critical roles in the pathogenesis of diabetes, hypertension, and atherosclerosis; some authors reported that fat accumulation correlates to systemic oxidative stress in human and mice, but cellular redox environment effect on lipid accumulation is still unclear. In our labora...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-10-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231716300386 |
| _version_ | 1819098954712743936 |
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| author | A. Pieralisi C. Martini D. Soto M.C. Vila J.C. Calvo L.N. Guerra |
| author_facet | A. Pieralisi C. Martini D. Soto M.C. Vila J.C. Calvo L.N. Guerra |
| author_sort | A. Pieralisi |
| collection | DOAJ |
| description | Oxidative stress plays critical roles in the pathogenesis of diabetes, hypertension, and atherosclerosis; some authors reported that fat accumulation correlates to systemic oxidative stress in human and mice, but cellular redox environment effect on lipid accumulation is still unclear. In our laboratory we used mouse embryonic fibroblasts (undifferentiated cells: CC), which are capable of differentiating into mature adipocytes (differentiated cells: DC) and accumulate lipids, as obesity model. Here we analyzed the role of the well-known antioxidant and glutathione precursor N-acetylcysteine (NAC) in cellular MAPK modulation and lipid accumulation. We evaluated the effect of NAC on the adipogenic differentiation pathway using different doses: 0.01, 0.1, 1 and 5 mM; no toxic doses in these cells. A dose of 5 mM NAC [DCN-5] provoked a significant decrease in triglyceride accumulation (72±10 [DCN-5] vs 169±15 [DC], p<0.01), as well in Oil Red O stained neutral lipid content (120±2 [DCN-5] vs 139±12 [DC], p<0.01). Molecular mechanisms responsible for adipogenic differentiation involve increase of the expression of phosphoERK½ and phosphoJNK, 5 mM NAC treatment inhibited both pERK½ and pJNK protein levels. We also evaluated the mitotic clonal expansion (MCE) which takes place during adipogenesis and observed an increase in DC at a rate of 1.5 cells number compared to CC at day 2, whereas the highest doses of NAC significantly inhibited MCE. Our results suggest that NAC inhibits lipid accumulation and the MAPK phosphorylation in mouse embryonic fibroblasts during adipogenic differentiation and further contribute to probe the importance of cellular redox environment in adipogenesis. |
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| id | doaj.art-f605f7bea5814e3fa369e540ed7deac2 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-22T00:39:12Z |
| publishDate | 2016-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-f605f7bea5814e3fa369e540ed7deac22022-12-21T18:44:44ZengElsevierRedox Biology2213-23172016-10-019C394410.1016/j.redox.2016.05.006N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytesA. Pieralisi0C. Martini1D. Soto2M.C. Vila3J.C. Calvo4L.N. Guerra5Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires – IQUIBICEN, CONICET, Intendente Güiraldes 2160, Pabellón 2, 1428 Buenos Aires, ArgentinaDepartamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires – IQUIBICEN, CONICET, Intendente Güiraldes 2160, Pabellón 2, 1428 Buenos Aires, ArgentinaDepartamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires – IQUIBICEN, CONICET, Intendente Güiraldes 2160, Pabellón 2, 1428 Buenos Aires, ArgentinaDepartamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires – IQUIBICEN, CONICET, Intendente Güiraldes 2160, Pabellón 2, 1428 Buenos Aires, ArgentinaIBYME, CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, ArgentinaDepartamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires – IQUIBICEN, CONICET, Intendente Güiraldes 2160, Pabellón 2, 1428 Buenos Aires, ArgentinaOxidative stress plays critical roles in the pathogenesis of diabetes, hypertension, and atherosclerosis; some authors reported that fat accumulation correlates to systemic oxidative stress in human and mice, but cellular redox environment effect on lipid accumulation is still unclear. In our laboratory we used mouse embryonic fibroblasts (undifferentiated cells: CC), which are capable of differentiating into mature adipocytes (differentiated cells: DC) and accumulate lipids, as obesity model. Here we analyzed the role of the well-known antioxidant and glutathione precursor N-acetylcysteine (NAC) in cellular MAPK modulation and lipid accumulation. We evaluated the effect of NAC on the adipogenic differentiation pathway using different doses: 0.01, 0.1, 1 and 5 mM; no toxic doses in these cells. A dose of 5 mM NAC [DCN-5] provoked a significant decrease in triglyceride accumulation (72±10 [DCN-5] vs 169±15 [DC], p<0.01), as well in Oil Red O stained neutral lipid content (120±2 [DCN-5] vs 139±12 [DC], p<0.01). Molecular mechanisms responsible for adipogenic differentiation involve increase of the expression of phosphoERK½ and phosphoJNK, 5 mM NAC treatment inhibited both pERK½ and pJNK protein levels. We also evaluated the mitotic clonal expansion (MCE) which takes place during adipogenesis and observed an increase in DC at a rate of 1.5 cells number compared to CC at day 2, whereas the highest doses of NAC significantly inhibited MCE. Our results suggest that NAC inhibits lipid accumulation and the MAPK phosphorylation in mouse embryonic fibroblasts during adipogenic differentiation and further contribute to probe the importance of cellular redox environment in adipogenesis.http://www.sciencedirect.com/science/article/pii/S2213231716300386N-acetylcysteineAntioxidantsMEFAdipogenesisKinasesLipids |
| spellingShingle | A. Pieralisi C. Martini D. Soto M.C. Vila J.C. Calvo L.N. Guerra N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes Redox Biology N-acetylcysteine Antioxidants MEF Adipogenesis Kinases Lipids |
| title | N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes |
| title_full | N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes |
| title_fullStr | N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes |
| title_full_unstemmed | N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes |
| title_short | N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes |
| title_sort | n acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes |
| topic | N-acetylcysteine Antioxidants MEF Adipogenesis Kinases Lipids |
| url | http://www.sciencedirect.com/science/article/pii/S2213231716300386 |
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