Dietary fat has been correlated with obesity since it induces the proliferation and differentiation of pre-adipocytes. However it has become clear that the effect of fat on human health depends on the composition and the nature of fatty acids. Arachidonic acid (AA) is a major omega-6 polyunsaturated fatty acid (PUFA) with a controversial role in adipocyte differentiation. We investigated the effect of a brief AA exposure on pre-adipocyte differentiation. We show that a short treatment of 3T3-L1 cells with AA at the start of differentiation induces events with a long lasting inhibitory effect on adipogenesis. Treatment of pre-adipocytes with AA for only 24h prevented differentiation since the expression of adipocyte markers (PPARγ, c/EBPα, aP2 etc.) and lipid accumulation were significantly reduced after 10 days of differentiation. In addition, after 24h of differentiation in the presence of AA treatment the expression of aP2 and Fra-1, an AP-1 transcription factor, was induced. We show that this effect is PPARγ -dependent since AA treatment was unable to induce aP2 and Fra-1 upregulation in PPARγ knockdown cells. Treatment with a COX inhibitor and also a MEK inhibitor blocked AA action on aP2 and Fra-1 expression indicating that AA effect is prostaglandin and MAPK-mediated. We suggest that a short treatment with AA during the early stages of adipocyte differentiation regulates PPARγ expression and/or activity with two very different outcomes. On the one hand, PPARγ in the presence of AA causes the rapid upregulation of two target genes aP2 and Fra-1. On the other hand, at the later stages of differentiation in the absence of AA, PPARγ expression fails to be induced and initiate the differentiation program.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: Declaration of Funding: Genesis Research Trust (292518).