Overnutrition and genetic predisposition are major risk factors for various metabolic
disorders. Stearoyl-CoA desaturase-1 (SCD1) plays a key role in these conditions by
synthesizing unsaturated fatty acids (FAs), thereby promoting fat storage and alleviating
lipotoxicity. Expression of SCD1 is influenced by various saturated and cis-unsaturated
FAs, but the possible role of dietary trans FAs (TFAs) and SCD1 promoter polymorphisms
in its regulations has not been addressed. Therefore, we aimed to investigate the
impact of the two main TFAs, vaccenate and elaidate, and four common promoter polymorphisms
(rs1054411, rs670213, rs2275657, rs2275656) on SCD1 expression in HEK293T and HepG2
cell cultures using luciferase reporter assay, qPCR and immunoblotting. We found that
SCD1 protein and mRNA levels as well as SCD1 promoter activity are markedly elevated
by elaidate, but not altered by vaccenate. The promoter polymorphisms did not affect
the basal transcriptional activity of SCD1 . However, the minor allele of rs1054411
increased SCD1 expression in the presence of various FAs. Moreover, this variant was
predicted in silico and verified in vitro to reduce the binding of ETS1 transcription
factor to SCD1 promoter. Although we could not confirm an association with type 2
diabetes mellitus, the FA-dependent and ETS1-mediated effect of rs1054411 polymorphism
deserves further investigation as it may modulate the development of lipid metabolism-related
conditions.
