The Hypotriglyceridemic Effect of Sciadonic Acid is Mediated by the Inhibition of Δ9-Desaturase Expression and Activity.

ABSTRACT

SCOPE Sciadonic acid (Scia; 203Δ5,11,14) is a distinctive fatty acid (FA) with a polymethylene-interrupted double bond at C5. It is specifically found in seeds from gymnosperms such as pine nuts. Published papers describe a decrease in liver and plasma triacylglycerols in rats fed with this nutriment. The present study seeks to identify the action mechanism of Scia on triacylglycerol synthesis. In this way, its nutritional effect on FA metabolism involving the Stearoyl-CoA Desaturase 1 (SCD1) is investigated. METHODS AND RESULTS: Scia is discerned in trace amount in various tissues of rats and in human serum. It is produced by Δ5-desaturation of 202n-6 in human transfected SH-SY5Y cell lines and also in rat hepatocytes. When Scia is incubated with cultured hepatocytes as a nutrient, the cellular FA profile is modified. In particular, the proportion of the monoenes (181n-9, 181n-7, 161n-7) are all decreased, correlating to the reduction of triacylglycerol amounts. This effect is mediated by the inhibition of SCD1 expression. Furthermore, Scia, as well as 203n-6 and 203n-9 but not 203n-3, strongly inhibit the SCD1 activity measured on liver microsomes. CONCLUSION: Overall, this study shows that Scia, despite its unusual structure, contributes to the FA metabolism and reduced triacylglycerol release by inhibiting SCD1 activity.