Effects of retinoic acid and hydrogen peroxide on sterol regulatory element-binding protein-1a activation during adipogenic differentiation of 3T3-L1 cells

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Both retinoic acid (RA) and oxidative stress (H2O2) increased transcription and cleavage ofmembrane-bound sterol regulatory element-binding protein (SREBP)-1, leading toenhanced transcription of fatty acid synthase (FAS) in hepatoma cells. On the other hand,RA and H2O2 decreased and increased lipogenesis in adipocytes, respectively, althoughroles of SREBP-1 activation in these effects remain to be elucidated. To elucidate itsinvolvement, we examined the activation of SREBP-1a, expression of FAS genes and lipidaccumulation in 3T3-L1 cells in the presence of RA and/or H2O2. RA (1 μM) treatmentsuppressed expression of SREBP-1a and FAS genes and lipid accumulation. H2O2 (2 μM)treatment induced increased cleavage of SREBP-1a, without affecting amounts ofSREBP-1a mRNA and precursor protein, and enhanced expression of FAS gene and lipidaccumulation. Increased cleavage of SREBP-1a by H2O2 was also observed even in thepresence of RA. These results suggest that H2O2 enhances a cleavage of SREBP-1aprecursor protein, which independently occurs with the RA suppression of SREBP-1a geneexpression, and that RA itself has no role in the SREBP-1a activation in adipocytes.