Regulation of SCD1 expression by the polysiphonia morrowii extract

Abstract

SCD1 (Stearoyl-Coenzyme A desaturase 1) is the rate-limiting enzyme that catalyzes the synthesis of monounsaturated fatty acids from saturated fatty acids. The unsaturated fatty acids produced by SCD1 are essential for the biosynthesis of triglycerides. Increased SCD1 expression and activity has been implicated in many disease conditions as in obesity, insulin resistance, cardiovascular diseases, and cancer. Recently, it has been suggest that inhibition of SCD1 is a modality to control lipogenesis and body weight, and to treat obesity and hyperglyceridemia. In this study, the effect of the Polysiphonia morrowii extract on the plasma concentration of triglyceride was studied with regard to regulation of the SCD1 expression. Mice fed with a chow diet supplemented with the P. morrowii extract showed the lower plasma triglyceride level than that in control mice. Microarray analysis of mRNAs in livers revealed that the expression of Scd1 was down-regulated by the extract significantly. The reduced expression of Scd1 was confirmed by quantitative real-time PCR and Western blot analysis in livers of mice. The treatment HepG2 cells with the P. morrowii extract reduced both SCD1 mRNA and protein in a-dose dependent manner. In addition, the extract reduced the expression of the Scd1 mRNA and protein in 3T3-L1 cells during the process of differentiation from pre-adipocyte to adipocyte. The P. morrowii extract was able to repress the transcription of SCD1 regardless of mutations of conserved regulatory elements, such as LXRE, C/EBP, and SRE in the SCD1 promoter.In conclusion, the extract P. morrowii down-regulates the expression of SCD1 at the transcriptional level mediated by unidentified transcriptional factors, and it is suggested that the P. morrowii extract has the therapeutic potential for treatment of hyperglyceridemia by down-regulating the expression of SCD1.