👤 Mélanie Plourde

In a previous study, we showed that oral supplementation with lysophosphatidylcholine (LPC)-bound omega-3 fatty acids (n-3) increases cortical eicosapentaenoic acid (EPA, C20:5n-3) but not docosahexaenoic acid (DHA, C22:6n-3) in an apolipoprotein E (APOE)- and duration-dependent manner. This may reflect DHA retention in blood-brain interfaces, such as microvessels (MV) and choroid plexus (ChP). To assess whether LPC n-3 intake over two or four months modulates the lipid composition of MV and ChP in APOE3 and APOE4 mice. APOE3 and APOE4 mice received daily gavage of LPC-bound EPA (21.5 mg/day) and DHA (10.4 mg/day) or sunflower oil (control) for two or four months (n=5-8 mice per genotype and treatment). Lipids from plasma, frontal cortex (FCx), ChP, and MV were analyzed by liquid chromatography-tandem mass spectrometry. Principal component analysis indicated that phospholipid levels in plasma, ChP, MV and FCx were modulated more by the type of oil administered by gavage (LPC n-3-enriched oil vs. sunflower oil) than by APOE genotype or gavage duration. The ChP was the most responsive tissue to n-3 supplementation. Total DHA increased in the FCx of APOE3 mice receiving LPC n-3, but not in APOE4 mice. In contrast, EPA levels were significantly higher across genotypes and biological compartments in n-3-supplemented mice. This study reports higher DHA and EPA concentrations in the brain of APOE3 mice supplemented with LPC n‑3 and reinforces evidence of lower DHA accretion in APOE4 mice. It also identifies the ChP as a major site of n‑3 response. Show less

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two omega-3 fatty acids that can be synthesized out of their precursor alpha-linolenic acid (ALA). FADS and ELOVL genes encode the desaturase and elongase enzymes required for EPA and DHA synthesis from ALA; however, single nucleotide polymorphisms (SNPs) in FADS and ELOVL genes could modify the levels of EPA and DHA synthesized from ALA although there is no consensus in this area. This review aims to investigate EPA and DHA circulating levels in human blood and their association with FADS or ELOVL. PubMed, Cochrane, and Scopus databases were used to identify research articles. They were subsequently reviewed by two independent investigators. Initially, 353 papers were identified. After removing duplicates and articles not meeting inclusion criteria, 98 full text papers were screened. Finally, this review included 40 studies investigating FADS and/or ELOVL polymorphisms. A total of 47 different SNPs in FADS genes were reported. FADS1 rs174537, rs174547, rs174556 and rs174561 were the most studied SNPs, with minor allele carriers having lower levels of EPA and DHA. SNPs in the FADS genes were in high linkage disequilibrium. SNPs in FADS were correlated with levels of EPA and DHA. No conclusion could be drawn with the ELOVL polymorphisms since the number of studies was too low. Specific SNPs in FADS gene, such as rs174537, have strong associations with circulating levels of EPA and DHA. Continued investigation regarding the impact of genetic variants related to EPA and DHA synthesis is warranted. Show less

In both animals and plants, messenger (m)RNA export has been shown to contribute to immune response regulation. The Arabidopsis nuclear protein MOS11, along with the nucleoporins MOS3/Nup96/SAR3 and Nup160/SAR1 are components of the mRNA export machinery and contribute to immunity mediated by nucleotide binding leucine-rich repeat immune receptors (NLR). The human MOS11 ortholog CIP29 is part of a small protein complex with three additional members: the RNA helicase DDX39, ALY, and TAF15b. We systematically assessed the biological roles of the Arabidopsis homologs of these proteins in toll interleukin 1 receptor-type NLR (TNL)-mediated immunity using reverse genetics. Although mutations in ALY and DDX39 did not result in obvious defects, taf15b mutation partially suppressed the autoimmune phenotypes of a gain-of-function TNL mutant, snc1. An additive effect on snc1 suppression was observed in mos11-1 taf15b snc1 triple mutant plants, suggesting that MOS11 and TAF15b have independent functions. TAF15b-GFP fusion protein, which fully complemented taf15b mutant phenotypes, localized to nuclei similarly to MOS11. However, it was also targeted to cytosolic granules identified as processing bodies. In addition, we observed no change in SNC1 mRNA levels, whereas less SNC1 protein accumulated in taf15b mutant, suggesting that TAF15b contributes to SNC1 homeostasis through posttranscriptional mechanisms. In summary, this study highlights the importance of posttranscriptional RNA processing mediated by TAF15b in the regulation of TNL-mediated immunity. Show less

A family history and estrogen exposure are well-known risk factors for breast cancer. Members of the 17beta-hydroxysteroid dehydrogenase family are responsible for important steps in the metabolism of androgens and estrogens in peripheral tissues, including the mammary gland. The crucial biological function of 17beta-HSDs renders these genes good candidates for being involved in breast cancer etiology. This study screened for mutations in HSD17B7 and HSD17B12 genes, which encode enzymes involved in estradiol biosynthesis and in AKR1C3, which codes for 17beta-HSD type 5 enzyme involved in androgen and progesterone metabolism, to assess whether high penetrance allelic variants in these genes could be involved in breast cancer susceptibility. Mutation screening of 50 breast cancer cases from non-BRCA1/2 high-risk French Canadian families failed to identify germline likely high-risk mutations in HSD17B7, HSD17B12 and AKR1C3 genes. However, 107 sequence variants were identified, including seven missense variants. Assessment of the impact of missense variants on enzymatic activity of the corresponding enzymes revealed no difference in catalytic properties between variants of 17beta-HSD types 7 and 12 and wild-type enzymes, while variants p.Glu77Gly and p.Lys183Arg in 17beta-HSD type 5 showed a slightly decreased activity. Finally, a haplotype-based approach was used to determine tagging SNPs providing valuable information for studies investigating associations of common variants in these genes with breast cancer risk. Show less