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Nutrients Feb 2024Normal pregnancy involves numerous physiological changes, including changes in hormone levels, immune responses, and metabolism. Although several studies have shown that...
Normal pregnancy involves numerous physiological changes, including changes in hormone levels, immune responses, and metabolism. Although several studies have shown that the gut microbiota may have an important role in the progression of pregnancy, these findings have been inconsistent, and the relationship between the gut microbiota and metabolites that change dynamically during and after pregnancy remains to be clarified. In this longitudinal study, we comprehensively profiled the temporal dynamics of the gut microbiota, communities, and serum and faecal metabolomes of 31 women during their pregnancies and postpartum periods. The microbial composition changed as gestation progressed, with the pregnancy and postpartum periods exhibiting distinct bacterial community characteristics, including significant alterations in the genera of the Lachnospiraceae or Ruminococcaceae families, especially the and . Metabolic dynamics, characterised by changes in nutrients important for fetal growth (e.g., docosatrienoic acid), anti-inflammatory metabolites (e.g., trans-3-indoleacrylic acid), and steroid hormones (e.g., progesterone), were observed in both serum and faecal samples during pregnancy. Moreover, a complex correlation was identified between the pregnancy-related microbiota and metabolites, with and making important contributions to changes in faecal and serum metabolites, respectively. Overall, a highly coordinated microbiota-metabolite regulatory network may underlie the pregnancy process. These findings provide a foundation for enhancing our understanding of the molecular processes occurring during the progression of pregnancy, thereby contributing to nutrition and health management during this period.
Topics: Pregnancy; Humans; Female; Gastrointestinal Microbiome; Longitudinal Studies; Postpartum Period; Microbiota; Metabolome; Lactobacillales; RNA, Ribosomal, 16S
PubMed: 38398806
DOI: 10.3390/nu16040483 -
Journal of Biomolecular Structure &... Jan 2024is a Gram-negative, rod-shaped and opportunistic human pathogen. is resistant to various antibiotics due to the production of quorum sensing (QS)-controlled virulence...
is a Gram-negative, rod-shaped and opportunistic human pathogen. is resistant to various antibiotics due to the production of quorum sensing (QS)-controlled virulence factor and biofilm formation. Hence, we need to find alternative strategies to overcome the antimicrobial resistance and biofilm formation in Gram-negative bacteria. QS is a mechanism in which bacteria's ability to regulate the virulence factors and biofilm formations leads to disease progression. Previously, hexadecanoic acid was identified as a CviRmediated quorum-sensing inhibitor. In this study, we aimed to discover potential analogs of hexadecanoic acid as a CviR-mediated quorum-sensing inhibitor against by using ADME/T prediction, density functional theory, molecular docking, molecular dynamics and free energy binding calculations. ADME/T properties predicted for analogs were acceptable for human oral absorption and feasibility. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals gap energies predicted and found oleic acid with -0.3748 energies. Docosatrienoic acid exhibited the highest binding affinity -8.15 Kcal/mol and strong and stable interactions with the amino acid residues on the active site of the CviR protein. These compounds on MD simulations for 100 ns show strong hydrogen-bonding interactions with the protein and remain stable inside the active site. Our results suggest hexadecanoic acid analogs could serve as anti-QS and anti-biofilm molecules for treating infections. However, further validation and investigation of these inhibitors against CviR are needed to claim their candidacy for clinical trials.Communicated by Ramaswamy H. Sarma.
PubMed: 38165661
DOI: 10.1080/07391102.2023.2299945 -
Molecular Nutrition & Food Research Dec 2023Olive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on...
SCOPE
Olive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on hepatic lipid deposition have seldom been compared.
METHODS AND RESULTS
Ninety 8-week-old C57BL/6J male mice are randomly divided into six groups and fed diets containing lard, rapeseed oil, or olive oil with a 10% or 45% fat energy supply for 16 weeks. Under high-fat conditions, serum total cholesterol levels in the lard and olive oil groups are significantly higher than those in the rapeseed oil group. Hepatic lipid content in the olive oil group is higher than that in the other two groups. Compared with rapeseed oil, lard increases the liver levels of arachidonic, palmitic, and myristic acids and decreases the levels of eicosapentaenoic linolenic acid and linoleic acid. Olive oil increases the liver levels of docosatrienoic, arachidonic, oleic, and myristic acids; maltose; and fructose and decreases the levels of eicosapentaenoic, linolenic, and linoleic acids.
CONCLUSION
Olive oil probably causes hepatic lipid deposition in mice, which may enhance hepatic lipid synthesis by activating the starch and sucrose metabolic pathways. By contrast, rapeseed oil shows a significant anti-lipid deposition effect on the liver.
Topics: Male; Animals; Mice; Olive Oil; Rapeseed Oil; Cholesterol; Glucose; Lipid Metabolism; Transcriptome; Mice, Inbred C57BL; Dietary Fats; Liver; Fatty Acids, Monounsaturated; Myristic Acids; Plant Oils; Fatty Acids
PubMed: 37867207
DOI: 10.1002/mnfr.202300398 -
Plant Biotechnology Journal Jan 2023
Topics: Brassica; Metabolic Engineering; Fatty Acids, Omega-3; Fatty Acids, Unsaturated
PubMed: 36168772
DOI: 10.1111/pbi.13937 -
Biochemistry Jun 2021In this paper, human platelet 12-lipoxygenase [h12-LOX (ALOX12)], human reticulocyte 15-lipoxygenase-1 [h15-LOX-1 (ALOX15)], and human epithelial 15-lipoxygenase-2...
In this paper, human platelet 12-lipoxygenase [h12-LOX (ALOX12)], human reticulocyte 15-lipoxygenase-1 [h15-LOX-1 (ALOX15)], and human epithelial 15-lipoxygenase-2 [h15-LOX-2 (ALOX15B)] were observed to react with docosahexaenoic acid (DHA) and produce 17-hydroperoxy-4,7,10,13,15,19-docosahexaenoic acid (17S-HpDHA). The / values with DHA for h12-LOX, h15-LOX-1, and h15-LOX-2 were 12, 0.35, and 0.43 s μM, respectively, which demonstrate h12-LOX as the most efficient of the three. These values are comparable to their counterpart / values with arachidonic acid (AA), 14, 0.98, and 0.24 s μM, respectively. Comparison of their product profiles with DHA demonstrates that the three LOX isozymes produce 11S-HpDHA, 14S-HpDHA, and 17S-HpDHA, to varying degrees, with 17S-HpDHA being the majority product only for the 15-LOX isozymes. The effective / values (/ × percent product formation) for 17S-HpDHA of the three isozymes indicate that the value of h12-LOX was 2.8-fold greater than that of h15-LOX-1 and 1.3-fold greater than that of h15-LOX-2. 17S-HpDHA was an effective substrate for h12-LOX and h15-LOX-1, with four products being observed under reducing conditions: protectin DX (PDX), 16,17-epoxy-4,7,10,12,14,19-docosahexaenoic acid (16S,17S-epoxyDHA), the key intermediate in neuroprotection D1 biosynthesis [NPD1, also known as protectin D1 (PD1)], 11,17S-diHDHA, and 16,17S-diHDHA. However, h15-LOX-2 did not react with 17-HpDHA. With respect to their effective / values, h12-LOX was markedly less effective than h15-LOX-1 in reacting with 17S-HpDHA, with a 55-fold lower effective / in producing 16S,17S-epoxyDHA and a 27-fold lower effective / in generating PDX. This is the first direct demonstration of h15-LOX-1 catalyzing this reaction and reveals an pathway for PDX and NPD1 intermediate biosynthesis. In addition, epoxide formation from 17S-HpDHA and h15-LOX-1 was negatively affected via allosteric regulation by 17S-HpDHA ( = 5.9 μM), 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12S-HETE) ( = 2.5 μM), and 17-hydroxy-13,15,19-docosatrienoic acid (17S-HDTA) ( = 1.4 μM), suggesting a possible regulatory pathway in reducing epoxide formation. Finally, 17S-HpDHA and PDX inhibited platelet aggregation, with EC values of approximately 1 and 3 μM, respectively. The results presented here may help advise PDX and NPD1 intermediate (i.e., 16S,17S-epoxyDHA) biosynthetic investigations and support the benefits of DHA rich diets.
Topics: Allosteric Regulation; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Arachidonic Acid; Arachidonic Acids; Biosynthetic Pathways; Blood Platelets; Docosahexaenoic Acids; Humans; Lipoxygenase; Lipoxygenases
PubMed: 34029049
DOI: 10.1021/acs.biochem.0c00931 -
Metabolic Engineering Communications Jun 2021Docosadienoic acid (DDA, 22:2-13,16) and docosatrienoic acid (DTA, 22:3-13,16,19) are two very long chain polyunsaturated fatty acids (VLCPUFAs) that are recently shown...
Docosadienoic acid (DDA, 22:2-13,16) and docosatrienoic acid (DTA, 22:3-13,16,19) are two very long chain polyunsaturated fatty acids (VLCPUFAs) that are recently shown to possess strong anti-inflammatory and antitumor properties. An ELO type elongase (EhELO1) from wild plant can synthesize the two fatty acids by sequential elongation of linoleic acid and alpha-linolenic acid, respectively. Seed-specific expression of this gene in oilseed crop produced a considerable amount of DDA and DTA in transgenic seeds. However, these fatty acids were excluded from the position of triacylglycerols (TAGs). To improve the production level and nutrition value of the VLCPUFAs in the transgenic oilseed crop, a cytoplasmic lysophosphatidic acid acyltransferase (EhLPAAT2) for the incorporation of the two fatty acids into the -2 position of triacylglycerols was identified from . RT-PCR analysis showed that it was preferentially expressed in developing seeds where was exclusively expressed in . Seed specific expression of along with in resulted in the effective incorporation of DDA and DTA at the position of TAGs, thereby increasing the total amount of DDA and DTA in transgenic seeds. To our knowledge, this is the first plant LPAAT that can incorporate VLCPUFAs into TAGs. Improved production of DDA and DTA in the oilseed crop using EhLPAAT2 and EhELO1 provides a real commercial opportunity for high value agriculture products for nutraceutical uses.
PubMed: 34026531
DOI: 10.1016/j.mec.2021.e00171 -
AMB Express Mar 2021The basidiomycetous lipoxygenase Lox1 from Cyclocybe aegerita catalyzes the oxygenation of polyunsaturated fatty acids (PUFAs) with a high preference towards the...
The basidiomycetous lipoxygenase Lox1 from Cyclocybe aegerita catalyzes the oxygenation of polyunsaturated fatty acids (PUFAs) with a high preference towards the C18-PUFA linoleic acid (C18:2 (ω-6)). In contrast, longer PUFAs, generally not present in the fungal cell such as eicosatrienoic acid (C20:3(ω-3)) and docosatrienoic acid (C22:3 (ω-3)), are converted with drastically lower activities. With site-directed mutagenesis, we were able to create two variants with enhanced activities towards longer chain PUFAs. The W330L variant showed a ~ 20 % increased specific activity towards C20:3(ω-3), while a ~ 2.5-fold increased activity against C22:3 (ω-3) was accomplished by the V581 variant.
PubMed: 33661405
DOI: 10.1186/s13568-021-01195-8 -
Nutrition and Cancer 2021Very long chain polyunsaturated fatty acids (VLCPUFAs) are widely used as nutraceutical supplements for human health. Recently, a high level of two new VLCPUFAs,...
Comparing the In Vitro Antitumor, Antioxidant and Anti-Inflammatory Activities between Two New Very Long Chain Polyunsaturated Fatty Acids, Docosadienoic Acid (DDA) and Docosatrienoic Acid (DTA), and Docosahexaenoic Acid (DHA).
Very long chain polyunsaturated fatty acids (VLCPUFAs) are widely used as nutraceutical supplements for human health. Recently, a high level of two new VLCPUFAs, docosadienoic acid (DDA, 22:2n-6) and docosatrienoic acid (DTA, 22:3n-3), was produced in oilseed crop using a biotechnology approach. This study investigated the functional properties of these two VLCPUFAs in human cells. Compared to docosahexaenoic acid (DHA), the golden standard in evaluating the health-promoting activities of VLCPUFAs, both DDA and DTA exhibited comparable or even better antitumor and antioxidant effects against human breast cancer SK-BR-3 and MDA-MB-231 cells. Especially, DTA elicited much stronger antioxidant and pro-apoptotic effects than DHA. Furthermore, DDA and DTA showed strong anti-inflammatory effects in human macrophages differentiated from monocyte THP-1 cells through lowering the protein expression levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon γ (IFN-γ), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNF-α). Future In Vivo and In Vivo studies are warranted to identify the mechanism of action (MOA) for the antitumor, antioxidant and anti-inflammatory functions of DDA and DTA and explore potential applications of these two VLCPUFAs as novel nutraceutical supplements in preventing inflammatory conditions, aging and even cancer.
Topics: Anti-Inflammatory Agents; Antioxidants; Docosahexaenoic Acids; Fatty Acids, Unsaturated; Humans; Macrophages
PubMed: 32781843
DOI: 10.1080/01635581.2020.1804949 -
International Journal of Epidemiology Feb 2020Metabolomics profiling has shown promise in elucidating the biological pathways underpinning mortality, but there are limited data in female populations.
BACKGROUND
Metabolomics profiling has shown promise in elucidating the biological pathways underpinning mortality, but there are limited data in female populations.
METHODS
We applied a liquid chromatography-tandem mass spectrometry metabolomics platform to EDTA-plasma to measure 470 metabolites at baseline in a discovery set of 943 postmenopausal women (including 417 incident deaths, median time to death of 10.6 years) with validation in an independent set of 1355 postmenopausal women (including 685 deaths, median time to death of 9.1 years) in the Women's Health Initiative.
RESULTS
Eight new metabolites were discovered to be associated with all-cause mortality. Findings included protective effects of increased levels of three amino acids (asparagine, homoarginine and tryptophan) and docosatrienoic acid; and detrimental effects of increased levels of C4-OH-carnitine, hexadecanedioate and two purine/pyrimidines (N2, N2-dimethylguanosine and N4-acetylcytidine). In addition, a set of nine previously published metabolite associations were replicated. A metabolite score comprising 17 metabolites was associated with mortality (P < 10-8) after adjustment for risk factors, with a hazard ratio of 1.95 (95% CI: 1.46-2.62) for women in the highest quartile compared with the lowest quartile of metabolite score. The score was robust among younger women and older women, for both cardiovascular and non-cardiovascular mortality, and associated with both early deaths (within the first 10 years of baseline) and later deaths.
CONCLUSIONS
Our study fills a gap in the literature by identifying eight novel metabolite associations with all-cause mortality in women, using a robust study design involving independent discovery and validation datasets.
Topics: Aged; Cardiovascular Diseases; Chromatography, Liquid; Female; Humans; Metabolomics; Middle Aged; Postmenopause; Purines; Pyrimidines; Tandem Mass Spectrometry; Women's Health
PubMed: 31651959
DOI: 10.1093/ije/dyz211 -
Food Science & Nutrition Sep 2019The aim of the present work was to investigate the effects of feeding regimens (pasture vs. mixed diet) on meat quality, fatty acids, volatile compounds, and antioxidant...
The aim of the present work was to investigate the effects of feeding regimens (pasture vs. mixed diet) on meat quality, fatty acids, volatile compounds, and antioxidant properties in lamb meat. In total, 24 lambs were allotted into two feeding regimens at 10.23 kg live weight. Lambs were fed on pasture grass (PG group, = 12) or mixed diet (M group, = 12). (LT) muscle samples from the M group had a higher intramuscular fat (IMF) ( < 0.05), pHvalue ( < 0.01), and ash ( < 0.05) than the PG group. In contrast, the shear force ( < 0.05), L*( < 0.05), and b* ( < 0.001) in M group were lower than in PG group. Analyses indicated that PG group contained higher linolenic acid (C18:3n3) and docosatrienoic acid (C22:3n6) ( < 0.05) than the M group. Major volatile compounds in the muscles included hexanal, heptanal, nonanal, octanal, 1-pentanol, 1-hexanol, 1-octen-3-ol, and 2,3-octanedione. The levels of hexanal, nonanal, and 2,3-octanedione were significantly lower in PG lamb muscle ( < 0.01). In contrast, 1-pentanol and 1-hexanol levels were higher in M lamb muscle ( < 0.01). Muscle from PG lamb exhibited higher catalase (CAT) and glutathione peroxidase (GPx) activity ( < 0.05). PG muscle also contained a higher radical-scavenging ability (RSA; < 0.001) and cupric-reducing antioxidant capacity (CUPRAC; < 0.05). Overall, the improved antioxidant status in PG muscle inhibited lipid peroxidation (aldehydes and ketones), thereby improving the meat quality.
PubMed: 31572572
DOI: 10.1002/fsn3.1039