The fatty acid desaturase 3 gene encodes for different FADS3 protein isoforms in mammalian tissues

Pédrono, Frédérique; Blanchard, H.; Kloareg, Maëla; d’Andréa, Sabine; Daval, Stéphanie; Rioux, Vincent; Legrand, Philippe

doi:10.1194/jlr.m000588

Cited by 40 publications

(46 citation statements)

References 26 publications

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“…2), which encode for D5-and D6-fatty acid desaturase activities (involved in polyunsaturated fatty acid biosynthesis), respectively, and FADS3, whose function has not been established yet (Pedrono et al 2010). Although the mRNA levels for FADS1 and FADS2 were not detected under our experimental conditions, we observed a relative decrease in Fig.…”

Section: Diet and Fatty Acid Desaturation In Adipose Tissuementioning

confidence: 52%

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

et al. 2014

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Adipose tissue (AT) is a key organ in the regulation of total body lipid homeostasis, which is responsible for the storage and release of fatty acids according to metabolic needs. We aimed to investigate the effect of the quantity and quality of dietary fat on the lipogenesis and lipolysis processes in the AT of metabolic syndrome (MetS) patients. A randomized, controlled trial conducted within the LIPGENE study assigned MetS patients to one of four diets: (a) high-saturated fatty acid (HSFA) (b) highmonounsaturated fatty acid, and (c, d) two low-fat, highcomplex carbohydrate diets supplemented with long chain (LC) n-3 (LFHCC n-3) polyunsaturated fatty acids (PUFA) or placebo (LFHCC), for 12 weeks each. A fat challenge reflecting the same fatty acid composition as the original diets was conducted post-intervention. Long-term consumption of the LFHCC diet induced an increase in the fasting expression levels of the sterol regulatory element binding protein-1 and stearoyl-CoA desaturase D9-desaturase genes, whereas the supplementation of this diet with n-3 PUFA reversed this effect (p = 0.007). In contrast, long-term consumption of the HSFA diet increased the expression of the adipose triglyceride lipase (ATGL) gene, at both fasting and postprandial states (both, p \ 0.001). Our results showed the anti-lipogenic effect exerted by LC n-3 PUFA when administered together with a LFHCC diet. Conversely, a diet high in saturated fat increased the expression of the lipolytic gene ATGL relative to the other diets.

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Section: Diet and Fatty Acid Desaturation In Adipose Tissuementioning

confidence: 52%

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

et al. 2014

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“…FADS3 mRNA was shown to be ubiquitously expressed in a large variety of tissues in humans ( 7 ), baboons ( 12 ), and rats ( 11 ), with a specifi c distribution compared with FADS1 and FADS2 mRNAs. In neonate baboon tissues, seven alternative transcripts of FADS3 were described ( 12 ), but when they were cloned and expressed into yeast and mammalian cells, no activity toward a variety of PUFA substrates was detected ( 16 ).…”

Section: Fatty Acid Analysismentioning

confidence: 99%

“…The plasmids constructed for expressing rat FADS2 (pCMV/ FADS2) and FADS3 (pCMV/FADS3) in mammalian cells have been described ( 11,24 ). A plasmid coding for rat FADS1 was also constructed.…”

Section: Plasmid Constructs For Expressing Rat Fads1 Fads2 and Fadsmentioning

confidence: 99%

“…RNA was quantifi ed by real-time PCR with the Taqman Universal PCR Master Mix (Applied Biosystems) containing 40 ng of retrotranscripted RNA, 0.5 µM of primers, and 0.25 µM of Taqman probe. Primers and 5 ′ -FAM/TAMRA-3 ′ Taqman probes specifi c to each rat FADS gene were described previously ( 11 ). Primers (forward primer 5 ′ -caaagagaagggcggaaagc-3 ′ ; reverse primer 5 ′ -aaagtttcgccccagcagta-3 ′ ) and a Taqman probe (5 ′ FAMctggcctcctgctcatgtgcttca-TAMRA3 ′ ) were also designed to quantify SCD1 mRNA.…”

Section: Rna Isolation and Quantitative Rt-pcrmentioning

confidence: 99%

“…The pure trans 11, trans 13-18:2 was obtained from Larodan (Malmö, Sweden). [1][2][3][4][5][6][7][8][9][10][11][12][13] C] trans -vaccenic acid (chemical purity 95%, isotopic enrichment 99%) was synthesized by the Commissariat à l'Energie Atomique (CEA, Gif-sur-Yvette, France) according to well-established procedures ( 27,28 ). FA albuminic complexes were prepared as described ( 26 ).…”

Section: Incubation Of Cells With Fatty Acidsmentioning

confidence: 99%

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Trans-vaccenate is Δ13-desaturated by FADS3 in rodents

Rioux

Pédrono

Blanchard

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org "methyl-end" FA desaturases. Therefore, linoleic acid and ␣ -linolenic acid must be provided by the diet ( 3 ). These dietary essential FAs then serve as precursors for longer PUFAs of the n-6 and n-3 series, including arachidonic acid (20:4 n-6) and docosahexaenoic acid (22:6 n-3) required for many important physiological functions in humans ( 4,5 ). In this PUFA biosynthesis, only "front-end" desaturases ( ⌬ 5-and ⌬ 6-desaturases) are involved to introduce new double bonds between the preexisting double bonds and the carboxyl end of FAs ( 6 ).In 2000, the genomic structure of the fatty acid desaturase (FADS) cluster, located on chromosome 11 in humans, was reported ( 7 ). This cluster includes the FADS1 and FADS2 genes that code, respectively, for the well-known ⌬ 5-and ⌬ 6-desaturases involved in PUFA biosynthesis ( 8-10 ). A third gene was identifi ed on this cluster with high degree of nucleotide sequence homology with both FADS1 (62%) and FADS2 (70%) and was therefore named FADS3. Since its fi rst description in humans ( 7 ), FADS3 has been identifi ed in rats ( 11 ), baboons ( 12 ), mice ( 3 ), and many other mammals showing a similar nucleotide sequence and intron/exon organization ( 12 ). When analyzing the peptide sequence deduced from the FADS3 nucleotide sequence, FADS3 protein was identifi ed as a putative desaturase, according to its similarity with FADS1 and FADS2. Indeed, the predicted structure of FADS3 is composed of an N-terminal cytochrome b5-like domain characterized by a HPGG motif shown to be essential for the ⌬ 6-desaturase activity of FADS2 ( 13 ) QIEHH in the rat) characteristic of front-end-desaturases ( 14 ). According to its amino acid sequence, FADS3 was thereafter supposed to Abstract 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 ( ⌬ 5-desaturase) and FADS2 ( ⌬ 6-desaturase). Here, we show that rat FADS3 displays no common ⌬ 5-, ⌬ 6-or ⌬ 9-desaturase activity but is able to catalyze the unexpected ⌬ 13-desaturation of trans -vaccenate. Although there is no standard for complete conclusive identifi cation, structural characterization strongly suggests that the ⌬ 11,13-conjugated linoleic acid (CLA) produced by FADS3 from trans -vaccenate is the trans 11, cis 13-CLA isomer. In rat hepatocytes, knockdown of FADS3 expression specifically reduces trans -vaccenate ⌬ 13-desaturation. Evidence is presented that FADS3 is the fi rst "methyl-end" fatty acid desaturase functionally characterized in mammals. FA desaturases introduce double bonds between defi ned carbons of the fatty acyl chain and catalyze ...

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

Blanchard

Boulier-Monthéan

Legrand

et al. 2013

J of Cellular Biochemistry

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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.

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The fatty acid desaturase 3 gene encodes for different FADS3 protein isoforms in mammalian tissues

Cited by 40 publications

References 26 publications

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

Trans-vaccenate is Δ13-desaturated by FADS3 in rodents

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

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