Δ6-Desaturase (FADS2) deficiency unveils the role of ω3- and ω6-polyunsaturated fatty acids

Stoffel, Wilhelm; Holz, Barbara; Jenke, Britta; Binczek, Erika; Günter, Robert Heinz; Kiss, Christine; Karakesisoglou, Iakowos; Thevis, Mario; Weber, Artur‐Aron; Arnhold, Stephan; Addicks, Klaus

doi:10.1038/emboj.2008.156

Cited by 209 publications

(198 citation statements)

References 57 publications

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“…SCD is the enzyme catalysing two types of reactions: (i) biosynthesis of MUFA through the insertion of a double bound in SFAs between carbon C9 and C10 and (ii) the tissue biosynthesis of cis-9, trans-11 CLA from trans-vaccenic acid (Enoch et al, 1976). D6d is involved in a complex process of biosynthesis of longer chain n-3 and n-6 fatty acids through conversion of linoleic and linolenic acids to their products (Stoffel et al, 2008). The molecular weights of ACC, SCD and D6d immunoreactive bands detected in this study were 150, 37 and 50 kDa respectively, which is consistent with the molecular weights of ACC, SCD and D6d proteins reported for other species (Tanabe et al, 1975;Cho et al, 1999;Moreau et al, 2006).…”

Section: Discussionsupporting

confidence: 89%

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Herdmann

Nuernberg

Martin

et al. 2010

Animal

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This study investigated the effects of dietary linolenic acid (C18:3n-3) v. linoleic acid (C18:2n-6) on fatty acid composition and protein expression of key lipogenic enzymes, acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase (SCD) and delta 6 desaturase (Δ6d) in longissimus muscle and subcutaneous adipose tissue of bulls. Supplementation of the diet with C18:3n-3 was accompanied by an increased level of n-3 fatty acids in muscle which resulted in decrease of n-6/n-3 ratio. The diet enriched with n-3 polyunsaturated fatty acids (PUFAs) significantly inhibited SCD protein expression in muscle and subcutaneous adipose tissue, and reduced the Δ6d expression in muscle. There was no significant effect of the diet on ACC protein expression. Inhibition of the Δ6d expression was associated with a decrease in n-6 PUFA level in muscles, whereas repression of SCD protein was related to a lower oleic acid (C18:1 cis-9) content in the adipose tissue. Expression of ACC, SCD and Δ6d proteins was found to be relatively higher in subcutaneous adipose tissue when compared with longissimus muscle. It is suggested that dietary manipulation of fatty acid composition in ruminants is mediated, at least partially, through the regulation of lipogenic enzymes expression and that regulation of the bovine lipogenic enzymes expression is tissue specific.

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Section: Discussionsupporting

confidence: 89%

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Herdmann

Nuernberg

Martin

et al. 2010

Animal

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“…The PUFA are essential components of all cell membranes, and the proportions of various PUFA in the tissues of the reproductive tract reflect dietary consumption (Wathes et al 2007). Stoffel et al (2008) have used genetically modified mice that lacked the enzyme D6-FA desaturase, an enzyme that catalyzes the initial rate-limiting desaturation of C18:2n-6 and C18:3n-3 into long-chain PUFA, and found that the mice were viable but sterile. Furthermore, the D6-FA desaturase knock-out mice had smaller ovaries with lower blood supply than the control mice, and the multilayer granulosa cell syncytium, theca folliculi, and zona pellucida were absent, which demonstrated the essential role of long-chain PUFA in the development of the reproductive system (Stoffel et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Stoffel et al (2008) have used genetically modified mice that lacked the enzyme D6-FA desaturase, an enzyme that catalyzes the initial rate-limiting desaturation of C18:2n-6 and C18:3n-3 into long-chain PUFA, and found that the mice were viable but sterile. Furthermore, the D6-FA desaturase knock-out mice had smaller ovaries with lower blood supply than the control mice, and the multilayer granulosa cell syncytium, theca folliculi, and zona pellucida were absent, which demonstrated the essential role of long-chain PUFA in the development of the reproductive system (Stoffel et al 2008). Dietary PUFA can influence the reproductive processes through a variety of mechanisms; they provide the precursors for prostaglandin (PG) synthesis and can modulate the expression patterns of many key enzymes involved in both PG and steroid metabolism (Wathes et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Incorporation of dietary n-3 fatty acids into ovarian compartments in dairy cows and the effects on hormonal and behavioral patterns around estrus

Zachut¹,

Arieli²,

Moallem³

2011

Reproduction

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The objective of this study was to examine the incorporation of dietary n-3 fatty acids (FAs) into ovarian compartments and the effects on hormonal and behavioral patterns around estrus. Multiparous 256-day pregnant cows were fed either a standard diet both prepartum and postpartum (PP) (control; nZ22) or supplemented with extruded flaxseed (E-FLAX) providing C18:3n-3 at 172.2 and 402.5 g/day per cow prepartum and PP respectively (nZ22). The estrous cycle was synchronized, and at day 7 of the cycle, the cows were injected with prostaglandin F 2a (PGF 2a ) and then subjected to 5 days of intensive examination. Compared with those in the control, in the E-FLAX group, the interval from PGF 2a injection to behavioral estrus peak tended to be longer (3.6 h; P!0.1), that to estradiol (E 2 ) peak was 6.5 h longer (P!0.03), and that to LH peak tended to be longer (5.3 h; P!0.07). The durations of behavioral estrus and E 2 surge were longer, and the area under the E 2 curve was greater in the E-FLAX cows. Afterward, 7-8 days following behavioral estrus, follicular fluids (FFs) from O7 mm follicles were aspirated. The proportions of n-3 FA increased in plasma, FF, and granulosa cells in the E-FLAX group. The concentrations of PGE 2 in the E 2 -active follicles tended to be lower in the E-FLAX cows (P!0.06). In conclusion, several modifications in hormonal and behavioral estrus patterns were demonstrated in cows fed n-3 FA, which might be attributed to alterations in membrane FA composition and partly mediated by lower PGE 2 synthesis.

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“…The remaining proteins for which R2 unique peptides were identified are listed in Table 1 (detailed peptide data are given in Supplementary Table 1, see section on supplementary data given at the end of this article). All four of the remaining proteins, UQCRC2, FADS2, SCCPDH and TSSK1, have been shown to be expressed in the mouse testis (Kueng et al 1997, Stoffel et al 2008, Guo et al 2011, and targeted mutations of Fads2 and Tssk1/Tssk2 have been shown to disrupt spermatogenesis (Stoffel et al 2008, Xu et al 2008, Shang et al 2010. Tssk1 is a testis-specific kinase gene that plays a role in spermatogenesis, and the encoded protein, therefore, stood out to us as a particularly interesting candidate PPP1CC2 interactor in the testis.…”

Section: Resultsmentioning

confidence: 99%

PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins TSSK1 and TSKS in the mouse testis

MacLeod¹,

Shang²,

Booth³

et al. 2014

Reproduction

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The mouse protein phosphatase gene Ppp1cc is essential for male fertility, with mutants displaying a failure in spermatogenesis including a widespread loss of post-meiotic germ cells and abnormalities in the mitochondrial sheath. This phenotype is hypothesized to be responsible for the loss of the testis-specific isoform PPP1CC2. To identify PPP1CC2-interacting proteins with a function in spermatogenesis, we carried out GST pull-down assays in mouse testis lysates. Amongst the identified candidate interactors was the testis-specific protein kinase TSSK1, which is also essential for male fertility. Subsequent interaction experiments confirmed the capability of PPP1CC2 to form a complex with TSSK1 mediated by the direct interaction of each with the kinase substrate protein TSKS. Interaction between PPP1CC2 and TSKS is mediated through an RVxF docking motif on the TSKS surface. Phosphoproteomic analysis of the mouse testis identified a novel serine phosphorylation site within the TSKS RVxF motif that appears to negatively regulate binding to PPP1CC2. Immunohistochemical analysis of TSSK1 and TSKS in the Ppp1cc mutant testis showed reduced accumulation to distinct cytoplasmic foci and other abnormalities in their distribution consistent with the loss of germ cells and seminiferous tubule disorganization observed in the Ppp1cc mutant phenotype. A comparison of Ppp1cc and Tssk1/2 knockout phenotypes via electron microscopy revealed similar abnormalities in the morphology of the mitochondrial sheath. These data demonstrate a novel kinase/phosphatase complex in the testis that could play a critical role in the completion of spermatogenesis.

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Δ6-Desaturase (FADS2) deficiency unveils the role of ω3- and ω6-polyunsaturated fatty acids

Cited by 209 publications

References 57 publications

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Effect of dietary fatty acids on expression of lipogenic enzymes and fatty acid profile in tissues of bulls

Incorporation of dietary n-3 fatty acids into ovarian compartments in dairy cows and the effects on hormonal and behavioral patterns around estrus

PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins TSSK1 and TSKS in the mouse testis

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