The 51 kDa FADS3 is Secreted in the ECM of Hepatocytes and Blood in Rat

Abstract

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.

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

“…Rat primary hepatocytes were isolated by a collagenase perfusion using Liberase (Sigma–Aldrich) as described in earlier work . Four hours after plating in Primaria dishes (100 mm diameter), cells were treated either with Scia (Lipidox, Stockholm, Sweden) or with 20:2n‐6.…”

“…Rat primary hepatocytes were isolated by a collagenase perfusion using Liberase (Sigma-Aldrich) as described in earlier work. [12] Four hours after plating in Primaria dishes (100 mm diameter), cells were treated either with Scia (Lipidox, Stockholm, Sweden) or with 20:2n-6. They were cultured in DMEM with or without 7% fetal bovine serum (FBS) and some of each were also enriched with insulin (1 μmol L -1 ).…”

Lack of association of SNPs from the FADS1-FADS2 gene cluster with major depression or suicidal behavior

“…These desaturases are key enzymes in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) such as docosahexaneoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) from shorter-chain precursor α-linolenic acid (ALA, 18:3n-3) and arachidonic acid (AA, 20:5n-6) from precursor linoleic acid (LA, 18:2n-6) (Sprecher, 1981). The FADS3 gene shares a high sequence similarity (Marquardt, Stohr, White, & Weber, 2000) but its function is less clear (Blanchard, Boulier-Monthean, Legrand, & Pedrono, 2014; Reardon et al, 2013). Genotyping studies report that genetic variants of FADS1-FADS2 , together with diet, affect levels of n-3 and n-6 LC-PUFAs in serum phospholipids (Koletzko, Demmelmair, Schaeffer, Illig, & Heinrich, 2008; Malerba et al, 2008; Schaeffer et al, 2006), plasma (Gillingham et al, 2013; Solakivi et al, 2013), erythrocytes (Harslof et al, 2013), and brain (Rizzi et al, 2013).…”