Stearoyl CoA desaturase 1 (SCD1) and Seipin: Important players in hepatic steatosis?

Abstract

BackgroundSCD1 is a lipogenic enzyme responsible for the formation of monounsaturated fatty acids, the main precursors of triglycerides. High SCD1 expression is associated with expansion of adipose tissue and ectopic fat accumulation (in various tissues). Seipin is the human Berardinelli‐Seip congenital lipodystrophy 2 gene product which regulates adipogenesis and lipid droplets (LD) formation but whose function remains to be elucidated.AimIn the present study we evaluated the role of SCD1 and seipin in LD formation in hepatic cells and the effect of SCD1 or Seipine deficiency in the lipogenesis and insulin pathways. The results were also validated in seipin‐deficient mice.MethodsIn human hepato‐carcinoma cell line (HepG2), the expression of the two proteins was either silenced. LD formation was monitored by confocal microscopy upon addition of oleate. Under these conditions was also evaluated the activation of insulin and lipogenesis signaling pathways.ResultsWe observed that silencing SCD1 in HepG2 cells decreases the number and the size of LD, does not affect the lipogenic gene expression, increases insulin sensitivity (pAKT and pERK1). While silencing seipin has an opposite effect in the number of LDs. The mice develop a major hepatic steatosis. But the seipin deficiency does not affect lipogenesis but increases the expression of SCD1 and CD36 (in both HepG2 cells and liver of KO mice). Surprisingly, it increases significantly the insulin sensitivity in HepG2 cellsConclusionOur study demonstrated for the first time that low seipin expression in hepatic cells is directly associated with the development of hepatic steatosis. Seipin function appears to be inversely associated with SCD1 function. Finally, our work also suggests that variation of SCD1 and seipin expression influence insulin responses in hepatic cells.