4.7 Article

N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes

Journal

REDOX BIOLOGY
Volume 9, Issue -, Pages 39-44

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2016.05.006

Keywords

N-acetylcysteine; Antioxidants; MEF; Adipogenesis; Kinases; Lipids

Funding

  1. Universidad de Buenos Aires, Argentina [UBACYT 20020130200160BA, 42/2013 - 2015]
  2. CONICET (Ministerio de Ciencia y Tecnica, Argentina)
  3. Universidad de Buenos Aires

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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 perpendicular to 10 [DCN-5] vs 169 perpendicular to 15 [DC], p < 0.01), as well in Oil Red 0 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 phosphoERK1/2 and phosphoJNK, 5 mM NAC treatment inhibited both pERK1/2 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. (C) 2016 The Authors. Published by Elsevier B.V.

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