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International Journal of Molecular... Aug 2023The GC-MS profiling of the endogenous oxylipins (Me/TMS) from cucumber ( L.) leaves, flowers, and fruit peels revealed a remarkable abundance of...
The GC-MS profiling of the endogenous oxylipins (Me/TMS) from cucumber ( L.) leaves, flowers, and fruit peels revealed a remarkable abundance of 16-hydroxy-9,12,14-octadecatrienoic acid (16-HOT). Incubations of homogenates from these organs with α-linolenic acid yielded 16()-hydroperoxide (16-HPOT) as a predominant product. Targeted proteomic analyses of these tissues revealed the presence of several highly homologous isoforms of the putative "9-lipoxygenase type 6". One of these isoenzymes (CsLOX3, an 877 amino acid polypeptide) was prepared by heterologous expression in and exhibited 16()- and 13()-lipoxygenase activity toward α-linolenic and linoleic acids, respectively. Furthermore, α-linolenate was a preferred substrate. The molecular structures of 16()-HOT and 16()-HPOT (Me or Me/TMS) were unequivocally confirmed by the mass spectral data, H-NMR, 2D H-H-COSY, TOCSY, HMBC, and HSQC spectra, as well as enantiomeric HPLC analyses. Thus, the vegetative CsLOX3, biosynthesizing 16()-HPOT, is the first 16()-LOX and ω3-LOX ever discovered. Eicosapentaenoic and hexadecatrienoic acids were also specifically transformed to the corresponding ω3()-hydroperoxides by CsLOX3.
Topics: Cucumis sativus; alpha-Linolenic Acid; Escherichia coli; Proteomics; Fatty Acids, Omega-3; Hydrogen Peroxide; Lipoxygenases
PubMed: 37629162
DOI: 10.3390/ijms241612977 -
Gut Pathogens Jul 2023Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has...
BACKGROUND
Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has been implicated in postmenopausal osteoporosis. In this study, to understand gut microbiota signatures and fecal metabolite changes in postmenopausal women with osteoporosis, 108 postmenopausal women were recruited for intestinal microbiota and fecal metabolite detection. Among these participants, 98 patients, who met the inclusion criteria, were divided into postmenopausal osteoporosis (PMO) and non-postmenopausal osteoporosis (non-PMO) groups based on bone mineral density (BMD). The compositions of gut bacteria and fungi were examined by 16 S rRNA gene sequencing and ITS sequencing, respectively. Meanwhile, fecal metabolites were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS).
RESULTS
We found that bacterial α-diversity and β-diversity were significantly altered in PMO compared to non-PMO patients. Interestingly, fungi composition showed larger changes, and the differences in β-diversity were more significant between PMO and non-PMO patients. Metabolomics analysis revealed that fecal metabolites, such as levulinic acid, N-Acetylneuraminic acid, and the corresponding signaling pathways were also changed significantly, especially in the alpha-Linolenic acid metabolism and selenocompound metabolism. The screened differential bacteria, fungi, and metabolites closely correlated with clinical findings between these two groups, for example, the bacterial genus, Fusobacterium, the fungal genus, Devriesia, and the metabolite, L-pipecolic acid, were significantly associated with BMD.
CONCLUSIONS
Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients' BMD and clinical findings. These correlations provide novel insights into the mechanism of PMO development, potential early diagnostic indicators, and new therapeutic approaches to improve bone health in postmenopausal women.
PubMed: 37415173
DOI: 10.1186/s13099-023-00553-0 -
Nutrients Oct 2023We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in... (Observational Study)
Observational Study Randomized Controlled Trial
Effects of Varied Omega-3 Fatty Acid Supplementation on Postpartum Mental Health and the Association between Prenatal Erythrocyte Omega-3 Fatty Acid Levels and Postpartum Mental Health.
We investigated the postpartum mental health of women who had consumed perilla oil or fish oil containing various omega-3 fatty acids for 12 weeks starting in mid-pregnancy. The association between fatty acids in maternal erythrocytes and mental health risk factors was also examined. Healthy Japanese primiparas in mid-pregnancy (gestational weeks 18-25) were randomly divided into two groups and consumed approximately 2.0 g/day of omega-3 fatty acids in either perilla oil (the ALA dose was 2.4 g/day) or fish oil (the EPA + DHA dose was 1.7 g/day) for 12 weeks. Maternal mental health was assessed using the Edinburgh Postnatal Depression Scale (EPDS) as the primary measure and the Mother-to-Infant Bonding Scale (MIBS) as the secondary measure. Data from an observational study were used as a historical control. Maternal blood, cord blood, and colostrum samples were collected for fatty acid composition analysis. In addition, completers of the observational studies were enrolled in a case-control study, wherein logistic regression analysis was performed to examine the association between maternal fatty acids and EPDS score. The proportion of participants with a high EPDS score (≥9) was significantly lower in the perilla oil group (12.0%, = 0.044) but not in the fish oil group (22.3%, = 0.882) compared with the historical control (21.6%), while the proportions between the former groups also tended to be lower ( = 0.059). No marked effect of omega-3 fatty acid intake was observed from the MIBS results. In the case-control study of the historical control, high levels of α-linolenic acid in maternal erythrocytes were associated with an EPDS score of <9 (odds ratio of 0.23, 95% confidence interval: 0.06, 0.84, = 0.018 for trend). The results of this study suggest that consumption of α-linolenic acid during pregnancy may stabilize postpartum mental health.
Topics: Female; Humans; Pregnancy; alpha-Linolenic Acid; Case-Control Studies; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; Mental Health; Postpartum Period; Vitamins
PubMed: 37892462
DOI: 10.3390/nu15204388 -
Scientific Reports Aug 2023Hashimoto thyroiditis is an autoimmune disease characterized by hypothyroidism and a high level of anti-thyroid autoantibodies. It has shown to negatively impact female...
Hashimoto thyroiditis is an autoimmune disease characterized by hypothyroidism and a high level of anti-thyroid autoantibodies. It has shown to negatively impact female fertility; however, the mechanisms are unclear. Ovarian follicular fluid appears to be the key to understanding how Hashimoto thyroiditis affecst fertility. Thus, we aimed to evaluated the metabolic profile of follicular fluid and antithyroid autoantibody levels in the context of Hashimoto thyroiditis. We collected follicular fluid from 61 patients, namely 38 women with thyroid autoantibody positivity and 23 women as negative controls, undergoing in vitro fertilization treatment. Follicular fluid samples were analyzed using metabolomics, and thyroid autoantibodies were measured. Fifteen metabolites with higher concentrations in the follicular fluid samples from Hashimoto thyroiditis were identified, comprising five possible affected pathways: the glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and sphingolipid metabolism pathways. These pathways are known to regulate ovarian functions. In addition, antithyroglobulin antibody concentrations in both serum and follicular fluid were more than tenfold higher in women with Hashimoto thyroiditis than in controls. Our data showed that the metabolic profile of follicular fluid is altered in women with Hashimoto thyroiditis, suggesting a potential mechanistic explanation for the association of this disease with female infertility.
Topics: Humans; Female; Hashimoto Disease; Follicular Fluid; Autoantibodies; Autoimmune Diseases; Metabolomics
PubMed: 37532758
DOI: 10.1038/s41598-023-39514-7 -
Frontiers in Pharmacology 2023Fatty acids are a major nutrient in dietary fat, some of which are ligands of long-chain fatty acid receptors, including G-protein-coupled receptor (GPR) 40 and GPR120....
Fatty acids are a major nutrient in dietary fat, some of which are ligands of long-chain fatty acid receptors, including G-protein-coupled receptor (GPR) 40 and GPR120. Pretreatment with GPR40 agonists enhanced the secretion of insulin in response to elevating blood glucose levels after glucose load in a diabetes model, but pretreatment with GPR120 agonist did not ameliorate postprandial hyperglycemia. This study examined whether oral administration of linoleic acid (LA), a GPR40 and GPR120 agonist, immediately before glucose load would affect the elevation of postprandial blood glucose levels in rats. Male rats and rats with type 1 diabetes administered streptozocin were orally administered LA, trilinolein, α-linolenic acid (α-LA), oleic acid, TAK-875, or TUG-891 immediately before glucose load. Blood glucose levels were measured before, then 15, 30, 60 and 120 min after glucose load. CACO-2 cells were used to measure the uptake of [C] α-MDG for 30 min with or without LA. Gastric content from rats administered LA was collected 15 and 30 min after glucose load, and blood samples were collected for measurement of glucagon-like peptide 1 (GLP-1) and cholecystokinin concentrations. The elevation of postprandial blood glucose levels was slowed by LA but not by trilinolein in rats without promotion of insulin secretion, and this effect was also observed in rats with type 1 diabetes. The uptake of α-MDG, an SGLT-specific substrate, was, however, not inhibited by LA. Gastric emptying was slowed by LA 15 min after glucose load, and GLP-1, but not cholecystokinin, level was elevated by LA 15 min after glucose load. TUG-891, a GPR120 agonist, ameliorated postprandial hyperglycemia but TAK-875, a GPR40 agonist, did not. Pretreatment with AH7614, a GPR120 antagonist, partially canceled the improvement of postprandial hyperglycemia induced by LA. α-LA, which has high affinity with GPR120 as well as LA, slowed the elevation of postprandial blood glucose levels, but oleic acid, which has lower affinity with GPR120 than LA, did not. Oral administration of LA immediately after glucose load ameliorated postprandial hyperglycemia due to slowing of gastric emptying via promotion of GLP-1 secretion. The mechanisms may be associated with GPR120 pathway.
PubMed: 37583904
DOI: 10.3389/fphar.2023.1197743 -
Life Sciences Jan 2024Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia... (Review)
Review
Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems.
Topics: Humans; Linoleic Acid; alpha-Linolenic Acid; Insulin Resistance; Fatty Acids; Cognitive Dysfunction; Dyslipidemias; Dementia
PubMed: 38123015
DOI: 10.1016/j.lfs.2023.122356 -
International Journal of Molecular... Apr 2024The plant-derived α-linolenic acid (ALA) is an essential n-3 acid highly susceptible to oxidation, present in oils of flaxseeds, walnuts, canola, perilla, soy, and... (Review)
Review
The plant-derived α-linolenic acid (ALA) is an essential n-3 acid highly susceptible to oxidation, present in oils of flaxseeds, walnuts, canola, perilla, soy, and chia. After ingestion, it can be incorporated in to body lipid pools (particularly triglycerides and phospholipid membranes), and then endogenously metabolized through desaturation, elongation, and peroxisome oxidation to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with a very limited efficiency (particularly for DHA), beta-oxidized as an energy source, or directly metabolized to C18-oxilipins. At this moment, data in the literature about the effects of ALA supplementation on metabolic syndrome (MetS) in humans are inconsistent, indicating no effects or some positive effects on all MetS components (abdominal obesity, dyslipidemia, impaired insulin sensitivity and glucoregulation, blood pressure, and liver steatosis). The major effects of ALA on MetS seem to be through its conversion to more potent EPA and DHA, the impact on the n-3/n-6 ratio, and the consecutive effects on the formation of oxylipins and endocannabinoids, inflammation, insulin sensitivity, and insulin secretion, as well as adipocyte and hepatocytes function. It is important to distinguish the direct effects of ALA from the effects of EPA and DHA metabolites. This review summarizes the most recent findings on this topic and discusses the possible mechanisms.
Topics: Metabolic Syndrome; Humans; alpha-Linolenic Acid; Animals; Fatty Acids, Unsaturated; Dietary Supplements; Insulin Resistance
PubMed: 38732139
DOI: 10.3390/ijms25094909 -
Journal of Animal Science Jan 2024Both n-6 and n-3 fatty acids (FA) have numerous significant physiological roles for mammals. The interplay between these families of FA is of interest in companion... (Review)
Review
Both n-6 and n-3 fatty acids (FA) have numerous significant physiological roles for mammals. The interplay between these families of FA is of interest in companion animal nutrition due to the influence of the n-6:n-3 FA ratio on the modulation of the inflammatory response in disease management and treatment. As both human and animal diets have shifted to greater consumption of vegetable oils rich in n-6 FA, the supplementation of n-3 FA to canine, feline, and equine diets has been advocated for. Although fish oils are commonly added to supply the long-chain n-3 FA eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), a heavy reliance on this ingredient by the human, pet food, and equine supplement industries is not environmentally sustainable. Instead, sustainable sourcing of plant-based oils rich in n-3 α-linolenic acid (ALA), such as flaxseed and camelina oils, emerges as a viable option to support an optimal n-6:n-3 FA ratio. Moreover, ALA may offer health benefits that extend beyond its role as a precursor for endogenous EPA and DHA production. The following review underlines the metabolism and recommendations of n-6 and n-3 FA for dogs, cats, and horses and the ratio between them in promoting optimal health and inflammation management. Additionally, insights into both marine and plant-based n-3 FA sources will be discussed, along with the commercial practicality of using plant oils rich in ALA for the provision of n-3 FA to companion animals.
Topics: Animals; Dogs; Horses; Cats; Fatty Acids, Omega-3; alpha-Linolenic Acid; Fatty Acids, Omega-6; Animal Feed; Diet; Animal Nutritional Physiological Phenomena
PubMed: 38776363
DOI: 10.1093/jas/skae143 -
Biomedicine & Pharmacotherapy =... Jul 2023Non-alcoholic fatty liver disease (NAFLD) is gradually becoming one of the most common and health-endangering diseases. Flaxseed powder (FLA) is rich in α-linolenic...
Non-alcoholic fatty liver disease (NAFLD) is gradually becoming one of the most common and health-endangering diseases. Flaxseed powder (FLA) is rich in α-linolenic acid, dietary fiber, lignans, and other active ingredients, which have lipid-lowering and anti-inflammatory effects. Here, we investigated whether the FLA improves host metabolism by gut bacteria modulation and further bile acid modulation in mice fed a high-fat diet. At the end of the experiment, we found that FLA can significantly reduce the body weight, body fat content, and serum TG, LDL-C, and TNF-α levels of mice, and improve liver steatosis. FLA intervention has a significant effect on preventing and regulating the gut flora disturbance caused by HFD. FLA intervention affects bile acid metabolism in the intestine and causes significant changes in functional bile acids, which can play a lipid-lowering and anti-inflammatory role by activating the intestinal Fxr- Fgfr4-Cyp7a1 and Tgr5-Tlr4-Tnfα pathways.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Bile Acids and Salts; Flax; Powders; Diet, High-Fat; Metabolic Networks and Pathways; Lipids; Mice, Inbred C57BL; Liver
PubMed: 37167728
DOI: 10.1016/j.biopha.2023.114864 -
Nutrients Dec 2023Oral cancer ranks sixth among Taiwan's top 10 cancers and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has...
Oral cancer ranks sixth among Taiwan's top 10 cancers and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. We examined the mechanisms underlying ALA inhibition of metastasis and induction of apoptotic cell death in oral squamous cell carcinoma (OSCC). Migration and invasion assays confirmed the cancer cells' EMT capabilities, whereas flow cytometry and Western blotting identified molecular pathways in OSCC. ALA dramatically reduced cell growth in a concentration-dependent manner according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, the expression of Twist and EMT-related proteins, the expression of MMP2/-9 proteins, and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation and then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; alpha-Linolenic Acid; Cytochromes c; Cell Line, Tumor; Apoptosis; Cell Proliferation; Head and Neck Neoplasms; Cell Movement; Epithelial-Mesenchymal Transition
PubMed: 38068849
DOI: 10.3390/nu15234992