The 51 kDa FADS3 is secreted in the ECM of hepatocytes and blood in rat.

The fatty acid desaturase (Fads) cluster is composed of three genes encoding for the Δ5- and Δ6-desaturases and FADS3. The two former proteins are involved in the fatty acid biosynthesis; the latter one shares a high sequence identity but has still no attributed function. In a previous work performed in rat, we described three isoforms of FADS3 expressed in a tissue-dependent manner. In the present study, we demonstrated a specific subcellular targeting depending on the isoform. In cultured hepatocytes, which mainly expressed the 51 kDa protein, FADS3 was unexpectedly present in the cytosolic fraction, but was also secreted in the extracellular matrix on fibronectin-containing fibers. The secretion pathway was investigated and we determined the presence of exosome-like vesicles on the FADS3-stained fibers. In parallel, FADS3 was detected in blood of hepatic vessel, and particularly in serum. In conclusion, this study demonstrated a very specific intra- and extracellular location of FADS3 in comparison with the Δ5- and Δ6-desaturases, suggesting a unique function for this putative desaturase, even if no activity has been yet identified neither in the extracellular matrix of hepatocytes nor in serum.

Trans-vaccenate is Δ13-desaturated by FADS3 in rodents.

Fatty acid desaturases play critical roles in regulating the biosynthesis of unsaturated fatty acids in all biological kingdoms. As opposed to plants, mammals are so far characterized by the absence of desaturases introducing additional double bonds at the methyl-end site of fatty acids. However, the function of the mammalian fatty acid desaturase 3 (FADS3) gene remains unknown. This gene is located within the FADS cluster and presents a high nucleotide sequence homology with FADS1 (Δ5-desaturase) and FADS2 (Δ6-desaturase). Here, we show that rat FADS3 displays no common Δ5-, Δ6- or Δ9-desaturase activity but is able to catalyze the unexpected Δ13-desaturation of trans-vaccenate. Although there is no standard for complete conclusive identification, structural characterization strongly suggests that the Δ11,13-conjugated linoleic acid (CLA) produced by FADS3 from trans-vaccenate is the trans11,cis13-CLA isomer. In rat hepatocytes, knockdown of FADS3 expression specifically reduces trans-vaccenate Δ13-desaturation. Evidence is presented that FADS3 is the first "methyl-end" fatty acid desaturase functionally characterized in mammals.

Sciadonic acid derived from pine nuts as a food component to reduce plasma triglycerides by inhibiting the rat hepatic Δ9-desaturase.

Sciadonic acid (Scia) is a Δ5-olefinic fatty acid that is particularly abundant in edible pine seeds and that exhibits an unusual polymethylene-interrupted structure. Earlier studies suggested that Scia inhibited the in vitro expression and activity of the Stearoyl-CoA Desaturase 1 (SCD1), the hepatic Δ9-desaturase involved in the formation of mono-unsaturated fatty acids. To confirm this hypothesis, rats were given 10% Scia in diets balanced out with n-6 and n-3 fatty acids. In those animals receiving the Scia supplement, monoene synthesis in the liver was reduced, which was partly attributed to the inhibition of SCD1 expression. As a consequence, the presence of Scia induced a 50% decrease in triglycerides in blood plasma due to a reduced level of VLDL-secreted triglycerides from the liver. In non-fasting conditions, results showed that Scia-induced inhibition of SCD1 led to a decrease in the proportions of 16:1n-7 and 18:1n-7 in the liver without impacting on the level of 18:1n-9, suggesting that only triglycerides with neosynthesized monoenes are marked out for release. In conclusion, this in vivo study confirms that Scia highly inhibits SCD1 expression and activity. The work was performed on normo-triglyceride rats over six weeks, suggesting promising effects on hyper-triglyceridemic models.

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

SCOPE: Sciadonic acid (Scia; 20:3Δ5,11,14) 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 20:2n-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 (18:1n-9, 18:1n-7, 16:1n-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 20:3n-6 and 20:3n-9 but not 20:3n-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.