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

Pédrono, Frédérique; Boulier-Monthéan, Nathalie; Boissel, Françoise; Ossemond, Jordane; Dévéhat, Françoise Lohézic-Le

doi:10.1002/mnfr.201700567

Cited by 8 publications

(13 citation statements)

References 35 publications

(62 reference statements)

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“…2), in particular in the liver as already reported 8,17 . The FA 16:2n-6 was undetected in the liver tissue whereas it was present in cultured hepatocytes as previously described 17 . Of all the observations, the most remarkable effect was on the monoenes.…”

Section: Resultssupporting

confidence: 72%

“…The second observation was that the Scia diet induced an overall increase in the n-6 FA proportion, such as 18:2n-6 or its derivatives (Supplemental Fig. 2), in particular in the liver as already reported 8,17 . The FA 16:2n-6 was undetected in the liver tissue whereas it was present in cultured hepatocytes as previously described 17 .…”

Section: Resultssupporting

confidence: 66%

“…Linoleic acid (18:2n-6) was the most abundant FA in the diets: its proportion (36% of total FA) is intermediate between rat maternal milk (around 25% of total FA) and standard rodent chow (50% of total FA). This formulation choice was made because of its expected increase in tissues following the ingestion of Scia 8,17 and also to avoid a potential damaging side effect from an excessive level of this FA. Oleic acid (18:1n-9) represented around 30% of the total FA in the diets, which is substantially higher than found in rat milk and chow (about 20% of total FA).…”

Section: Resultsmentioning

confidence: 99%

“…Lipids were extracted using Folch's method 21 and quantified after weight measurement. The FA profile was determined from FA methyl esters (FAME) as described previously 17 . In this procedure, lipids were saponified and FA were methylated to be analyzed on an Agilent gas chromatograph (7890) equipped with a BPX70 capillary column and coupled to a flame ionization detector (Agilent Technologies, Les Ulis, France).…”

Section: Animals Diets and Tissue Sampling All Handling Protocols Pmentioning

confidence: 99%

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

Pédrono

Boulier-Monthéan

Boissel

et al. 2020

Sci Rep

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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 normotriglyceride rats over six weeks, suggesting promising effects on hyper-triglyceridemic models. Sciadonic acid (Scia) is composed of an aliphatic chain with 20 carbons and 3 unsaturations (20:3Δ5,11,14). It is a Δ5-olefinic acid, a fatty acid (FA) group characterized by the presence of a polymethylene-interrupted double bond at C5, as distinct from the more common malonic structure. In the natural environment, Scia is specifically abundant in conifers, although it is also present in trace amounts with different other olefinic structures in slime molds 1 and certain marine invertebrates 2. Seven Δ5-olefinic acids are commonly found in gymnosperms and their composition profile provides a good marker of the plant phylogeny 3,4. Scia is particularly associated with the suborder Taxares, representing up to 26% of the total FA content in Podocarpus nagi 5. It is ubiquitously found in pine nuts, constituting up to 7% of the total FA in Pinus pinaster 6. As it is present in edible seeds and consumed as a nutrient, studies performed on rodent models have been carried out to determine its functional effect. Scia is incorporated in membranes when supplied to the cells and substitutes for arachidonic acid (20:4n-6) in phospholipids such as phosphatidylinositol 7. Consequently, this unusual FA integrates lipid metabolism resulting in the modulation of physiological functions. Scia supplemented to mammal cells induces synthesis of the uncommon 16:2n-6 (Δ7,10), which is subsequently elongated into linoleic acid (18:2n-6 or Δ9,12) 8,9. Scia then reduces the production of modulators causing inflammation that are derived from arachidonic acid 10-13. In rats fed with a Scia-enriched diet, triglyceride levels are lowered in the blood plasma and the liver 14-16. Previous work performed in vitro on hepatocytes showed that Scia inhibited ...

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Section: Resultssupporting

confidence: 72%

Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Animals Diets and Tissue Sampling All Handling Protocols Pmentioning

confidence: 99%

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

Pédrono

Boulier-Monthéan

Boissel

et al. 2020

Sci Rep

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“…We also used this method in the previous study of FADS2 to locate the domains and sites of FADS2 activity, but the conversion rates of recombinant FADS2s could not reach that of the wild-type. Therefore, we wondered whether there were any components (Bichi et al, 2012; Chen et al, 2016; Pedrono et al, 2018; Ralston et al, 2014) that hindered the synthesis of unsaturated fatty acids. R. Jeffcoat and M. R. Pollard (Jeffcoat & Pollard, 1977) pointed out in 1977 that there was an accumulation of stearic acid [8-(2-octyl-l-cyclopropenyl) octanoic acid, a C18 cyclopropenoid fatty acid] and apparent loss of OA in both tissues and lipids in cows’ milk.…”

Section: Introductionmentioning

confidence: 99%

Both Determinants of Allosteric and Active Sites Responsible for Catalytic Activity of Delta 12 Fatty Acid Desaturase by Domain Swapping

Shi

Tian

et al. 2019

Preprint

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Cheese lacks essential fatty acids (EFAs). Delta 12 fatty acid desaturase (FADS12) is a critical enzyme required for EFA biosynthesis in fermentation of the predominant strains of cheese. Previously, we identified the FADS12 gene and characterized its function for the first time in Geotrichum candidum, a dominant strain used to manufacture soft cheese with white rind. In this study, we analyzed the molecular mechanism of FADS12 function by swapping domains from Mortierella alpina and G. candidum that had, respectively, high and low oleic acid conversion rates. The results revealed three regions that are essential to this process, including regions from the end of the second transmembrane domain to the beginning of the third transmembrane domain, from the end of the third transmembrane domain to the beginning of the fourth transmembrane domain, and from the 30-amino acid from the end of the sixth transmembrane domain to the C-terminal end region. Based on our domain swapping analyses, nine pairs of amino acids including H112, S118, H156, Q161, K301, R306, E307, A309 and S323 in MaFADS12 (K123, A129, N167, M172, T302, D307, I308, E310 and D324 in GcFADS12) were identified as having a significantly effect on FADS12 catalytic efficiency, and linoleic acid and its analogues (12,13-cyclopropenoid fatty acid) were found to inhibit the catalytic activity of FADS12 and related recombinant enzymes. Furthermore, the molecular mechanism of FADS12 inhibition was analyzed. The results revealed two allosteric domains, including one domain from the N-terminal region to the beginning of the first transmembrane domain and another from the 31st amino acid from the end of the sixth transmembrane domain to the C terminus. Y4 and F398 amino acid residues from MaFADS12 and eight pairs of amino acids including G56, L60, L344, G10, Q13, S24, K326 and L344 in MaFADS12 (while Y66, F70, F345, F20, Y23, Y34, F327 and F345 in GcFADS12) played a pivotal role in FADS12 inhibition. Finally, we found that both allosteric and active sites were responsible for the catalytic activity of FADS12 at various temperatures, pH, and times. This study offers a solid theoretical basis to develop preconditioning methods to increase the rate at which GcFADS12 converts oleic and linoleic acids to produce higher levels of EFAs in cheese.

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Silver ion assisted urea complexation for the enrichment of sciadonic acid from Torreya fargesii kernel oil

Meng

Ding

2023

Biochemical Engineering Journal

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

Abstract: Overall, this study shows that Scia, despite its unusual structure, contributes to the FA metabolism and reduced triacylglycerol release by inhibiting SCD1 activity.

Cited by 8 publications

References 35 publications

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

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

Both Determinants of Allosteric and Active Sites Responsible for Catalytic Activity of Delta 12 Fatty Acid Desaturase by Domain Swapping

Silver ion assisted urea complexation for the enrichment of sciadonic acid from Torreya fargesii kernel oil

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