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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 -
Physiological Genomics Aug 2018Evidence shows that proteins secreted from skeletal muscle influence a broad range of metabolic signaling pathways. We previously reported that essential polyunsaturated...
Evidence shows that proteins secreted from skeletal muscle influence a broad range of metabolic signaling pathways. We previously reported that essential polyunsaturated fatty acids (PUFA) improved whole-body glucose homeostasis in obese Zucker rats; however, the mechanisms underlying these benefits remain enigmatic. While PUFA and obesity influence skeletal muscle function, their effects on the secretome are unknown. The aim of this work was to determine if improvements in whole-body glucose homeostasis in obese Zucker rats fed diets supplemented with either linoleic acid (LA) or alpha-linolenic acid (ALA) for 12 wk are related to changes in the skeletal muscle secretome. Secreted proteins were identified with a predictive bioinformatic analysis of microarray gene expression from red tibialis anterior skeletal muscle. Approximately 130 genes were differentially expressed (false discovery rate = 0.05) in obese rats compared with lean controls. The expression of 15 genes encoding secreted proteins was differentially regulated in obese controls, obese LA-supplemented, and obese ALA-supplemented rats compared with lean controls. Five secreted proteins ( Col3a1, Col15a1, Pdgfd, Lyz2, and Angptl4) were differentially regulated by LA and ALA. Most notably, ALA supplementation reduced Angptl4 gene expression compared with obese control and obese-LA supplemented rats and reduced circulating ANGPTL4 serum concentrations. ALA also influenced Angptl4 gene expression and ANGPTL4 secretion from differentiated rat L6 myotubes. Altogether, the present data indicate that obesity has a greater global impact on skeletal muscle gene expression than either essential PUFA; however, LA and ALA may exert their metabolic benefits in part by regulating the skeletal muscle secretome.
Topics: Animals; Computational Biology; Dietary Supplements; Gene Expression Profiling; Glucose; Homeostasis; Linoleic Acid; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Obesity; Protein Translocation Systems; Rats, Zucker; Transcriptome; alpha-Linolenic Acid
PubMed: 29727591
DOI: 10.1152/physiolgenomics.00038.2018 -
Brazilian Journal of Biology = Revista... 2021The objective of the current study was to investigate the synergistic impact of α-Tocopherol and α-Linolenic acid (100 µM) on IVM and IVC of Nili Ravi buffalo...
The objective of the current study was to investigate the synergistic impact of α-Tocopherol and α-Linolenic acid (100 µM) on IVM and IVC of Nili Ravi buffalo oocytes. Oocytes were obtained from the ovaries of slaughtered buffaloes within two hours after slaughter and brought to laboratory. Buffalo cumulus oocyte complexes were placed randomly in the five experimental groups included; GROUP 1: Maturation media (MM) + 100 µM ALA (control), GROUP 2: MM + 100 µM ALA + 50μM α-Tocopherol, GROUP 3: MM + 100 µM ALA + 100μM α-Tocopherol, GROUP 4: MM + 100 µM ALA + 200 μM α-Tocopherol and GROUP 5: MM + 100 µM ALA + 300 μM α-Tocopherol under an atmosphere of 5% CO2 in air at 38.5 °C for 22-24 h. Cumulus expansion and nuclear maturation status was determined (Experiment 1). In experiment 2, oocytes were matured as in experiment 1. The matured oocytes were then fertilized in Tyrode's Albumin Lactate Pyruvate (TALP) medium for about 20 h and cultured in synthetic oviductal fluid (SOF) medium to determine effect of α-Linolenic acid (100 µM) and α-Tocopherol in IVM medium on IVC of presumptive zygotes. To study the effect of α-Linolenic acid (100 µM) in IVM media and increasing concentration of α-tocopherol in the culture media on early embryo development (Experiment 3), the presumptive zygotes were randomly distributed into the five experimental groups with increasing concentration of α-tocopherol in culture media. Higher percentage of MII stage oocytes in experiment 1(65.2±2.0), embryos at morula stage in experiment 2 (30.4±1.5) and experiment 3 (22.2±2.0) were obtained. However, overall results for cumulus cell expansion, maturation of oocyte to MII stage and subsequent embryo development among treatments remain statistically similar (P > 0.05). Supplementation of α-tocopherol in maturation media having α-Linolenic acid and/or in embryo culture media did not further enhance in vitro maturation of oocyte or embryo production.
Topics: Animals; Buffaloes; Culture Media; Embryonic Development; Oocytes; alpha-Linolenic Acid; alpha-Tocopherol
PubMed: 34932678
DOI: 10.1590/1519-6984.253514 -
Frontiers in Public Health 2022This study aimed to investigate the association of α-linolenic acid (ALA; 18:3 ω-3) dietary intake with very short sleep duration (<5 h) in adults based on the CDC's...
OBJECTIVES
This study aimed to investigate the association of α-linolenic acid (ALA; 18:3 ω-3) dietary intake with very short sleep duration (<5 h) in adults based on the CDC's National Health and Nutrition Examination Survey data.
METHODS
Multinomial logistic regression was used to explore the association of ALA intake with very short sleep. To make the estimation more robust, bootstrap methods of 1,000 replications were performed. Rolling window method was used to investigate the trend of the odds ratios of very short sleep with age. A Kruskal-Wallis test was applied to estimate the differences in the ORs of very short sleep between genders and different age groups.
RESULTS
Compared with the first tertile, the ORs of very short sleep and the corresponding 95% CIs for the second and the third tertile of dietary ALA intake in males were 0.618 (0.612, 0.624) and 0.544 (0.538, 0.551), respectively, and in females were 0.575 (0.612, 0.624) and 0.432 (0.427, 0.437). In most cases, the differences between different ages were more significant than those between different sexes. Men's very short sleep odds ratios for the second tertile of ALA intake increased linearly with age before 60.
CONCLUSIONS
The risk of a very short sleep duration was negatively related to the dietary intake of ALA. The effect of ALA on very short sleep is significantly different among groups of different genders and ages.
Topics: Adult; Diet; Eating; Female; Humans; Male; Nutrition Surveys; Sleep; alpha-Linolenic Acid
PubMed: 36062128
DOI: 10.3389/fpubh.2022.986424 -
International Journal of Molecular... Jul 2023A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the...
A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the influence of a low ratio of LA/ALA intake on lipid metabolism and endogenous fatty acid distribution in obese patients remains elusive. In this investigation, 8-week-old C57BL/6J mice were randomly assigned to four groups: low-fat diet (LFD) as a control, high-fat diet (HFD), high-fat diet with a low LA/ALA ratio (HFD+H3L6), and high-fat diet with a high LA/ALA ratio (HFD+L3H6) for 16 weeks. Our results show that the HFD+H3L6 diet significantly decreased the liver index of HFD mice by 3.51%, as well as the levels of triacylglycerols (TGs) and low-density lipoprotein cholesterol (LDL-C) by 15.67% and 10.02%, respectively. Moreover, the HFD+H3L6 diet reduced the pro-inflammatory cytokines interleukin-6 (IL-6) level and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and elevated the level of superoxide dismutase (SOD) in the liver. The HFD+H3L6 diet also resulted in the downregulation of fatty acid synthetase () and sterol regulatory element binding proteins-1c () expression and the upregulation of peroxisome proliferator-activated receptor-α () and acyl-CoA oxidase 1 () gene expression in the liver. The low LA/ALA ratio diet led to a notable increase in the levels of ALA and its downstream derivative docosahexaenoic acid (DHA) in the erythrocyte, liver, perienteric fat, epididymal fat, perirenal fat, spleen, brain, heart, and gastrocnemius, with a strong positive correlation. Conversely, the accumulation of LA in abdominal fat was more prominent, and a high LA/ALA ratio diet exacerbated the deposition effect of LA. In conclusion, the low LA/ALA ratio not only regulated endogenous fatty acid levels but also upregulated and and downregulated and gene expression levels, thus maintaining lipid homeostasis. Optimizing dietary fat intake is important in studying lipid nutrition. These research findings emphasize the significance of understanding and optimizing dietary fat intake.
Topics: Mice; Animals; Fatty Acids; Lipid Metabolism; alpha-Linolenic Acid; Linoleic Acid; Mice, Obese; Peroxisome Proliferator-Activated Receptors; Sterol Regulatory Element Binding Protein 1; Mice, Inbred C57BL; Liver; Diet, High-Fat; Obesity
PubMed: 37569494
DOI: 10.3390/ijms241512117 -
Frontiers in Immunology 2022Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to...
INTRODUCTION
Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to antigens and is more pro-inflammatory than in younger adults. Lipids are involved centrally in immune function but there is limited information about how T cell lipid metabolism changes during the life course.
METHODS AND RESULTS
We investigated whether life stage alters fatty acid composition, lipid droplet content and α-linolenic acid (18:3ω-3) metabolism in human fetal CD3 T lymphocytes and in CD3 T lymphocytes from adults (median 41 years) and seniors (median 70 years). Quiescent fetal T cells had higher saturated (SFA), monounsaturated fatty acid (MUFA), and ω-6 polyunsaturated fatty acid (PUFA) contents than adults or seniors. Activation-induced changes in fatty acid composition differed between life stages. The principal metabolic fates of [C]18:3ω-3 were constitutive hydroxyoctadecatrienoic acid synthesis and β-oxidation and carbon recycling into SFA and MUFA. These processes declined progressively across the life course. Longer chain ω-3 PUFA synthesis was a relatively minor metabolic fate of 18:3ω-3 at all life stages. Fetal and adult T lymphocytes had similar lipid droplet contents, which were lower than in T cells from seniors. Variation in the lipid droplet content of adult T cells accounted for 62% of the variation in mitogen-induced CD69 expression, but there was no significant relationship in fetal cells or lymphocytes from seniors.
DISCUSSION
Together these findings show that fatty acid metabolism in human T lymphocytes changes across the life course in a manner that may facilitate the adaptation of immune function to different life stages.
Topics: Adult; Humans; Fatty Acids; alpha-Linolenic Acid; T-Lymphocytes; Fatty Acids, Omega-3; Fatty Acids, Monounsaturated; Fatty Acids, Omega-6
PubMed: 36582247
DOI: 10.3389/fimmu.2022.1079642 -
Molecules (Basel, Switzerland) Sep 2022α-Linolenic acid (ALA) is a natural essential fatty acid widely found in plant seed oils and beans, which shows positive anti-inflammatory and antiallergic effects. In...
α-Linolenic acid (ALA) is a natural essential fatty acid widely found in plant seed oils and beans, which shows positive anti-inflammatory and antiallergic effects. In our previous study, ALA was proven to bind tightly to the seven protein targets closely associated with allergic rhinitis (AR) by molecular docking, which indicates that ALA may have a potential role in the treatment of AR. A mouse model of AR induced by ovalbumin (OVA) was adopted in this study to explore the therapeutical effect and potential mechanism of ALA in treating AR. Results demonstrated that ALA remarkably relieved the nasal symptoms, reduced the OVA-sIgE level in the serum, relieved the histopathological injuries, and downregulated the mRNA expression levels of IL-6 and IL-1β in the nasal mucosa. ALA also remarkably moderated the imbalance of Th1/Th2 cells, increased the mRNA expression levels of T-bet and STAT1, and reduced GATA3 and STAT6. ALA was proven to have a substantial therapeutic effect on mice with AR, and the underlying mechanism was likely to be the regulation of Th1/Th2 imbalance through the JAK/T-bet/STAT1 and JAK/GATA3/STAT6 pathways. This study provides a specific experimental basis for the clinical use and drug development of ALA in the treatment of AR.
Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Nasal Mucosa; Ovalbumin; Plant Oils; RNA, Messenger; Rhinitis, Allergic; Th2 Cells; alpha-Linolenic Acid
PubMed: 36144628
DOI: 10.3390/molecules27185893 -
Molecules (Basel, Switzerland) Jul 2022The essential fatty acid alpha-linolenic acid (ALA) is present in high amounts in oils such as flaxseed, soy, hemp, rapeseed, chia, and perilla, while stearidonic acid... (Review)
Review
The essential fatty acid alpha-linolenic acid (ALA) is present in high amounts in oils such as flaxseed, soy, hemp, rapeseed, chia, and perilla, while stearidonic acid is abundant in echium oil. ALA is metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by desaturases and elongases in humans. The conversion of ALA to EPA and DHA is limited, and these long-chain n-3 polyunsaturated fatty acids (PUFAs) are mainly provided from dietary sources (fish and seafood). This review provides an overview of studies that explored the effects of dietary supplementation with ALA in obesity and related diseases. The obesity-associated changes of desaturase and elongase activities are summarized, as they could influence the metabolic conversion of ALA. Generally, supplementation with ALA or ALA-rich oils leads to an increase in EPA levels and has no effect on DHA or omega-3 index. According to the literature data, stearidonic acid could enhance conversion of ALA to long-chain n-3 PUFA in obesity. Recent studies confirm that EPA and DHA intake should be considered as a primary dietary treatment strategy for improving the omega-3 index in obesity and related diseases.
Topics: Animals; Diet; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Obesity; alpha-Linolenic Acid
PubMed: 35889342
DOI: 10.3390/molecules27144471 -
The Journal of Nutrition Nov 2020Soybean lecithin, a plant-based emulsifier widely used in food, is capable of modulating postprandial lipid metabolism. With arising concerns of sustainability,...
BACKGROUND
Soybean lecithin, a plant-based emulsifier widely used in food, is capable of modulating postprandial lipid metabolism. With arising concerns of sustainability, alternative sources of vegetal lecithin are urgently needed, and their metabolic effects must be characterized.
OBJECTIVES
We evaluated the impact of increasing doses of rapeseed lecithin (RL), rich in essential α-linolenic acid (ALA), on postprandial lipid metabolism and ALA bioavailability in lymph-cannulated rats.
METHODS
Male Wistar rats (8 weeks old) undergoing a mesenteric lymph duct cannulation were intragastrically administered 1 g of an oil mixture containing 4% ALA and 0, 1, 3, 10, or 30% RL (5 groups). Lymph fractions were collected for 6 h. Lymph lipids and chylomicrons (CMs) were characterized. The expression of genes implicated in intestinal lipid metabolism was determined in the duodenum at 6 h. Data was analyzed using either sigmoidal or linear mixed-effects models, or one-way ANOVA, where appropriate.
RESULTS
RL dose-dependently increased the lymphatic recovery (AUC) of total lipids (1100 μg/mL·h per additional RL%; P = 0.010) and ALA (50 μg/mL·h per additional RL%; P = 0.0076). RL induced a faster appearance of ALA in lymph, as evidenced by the exponential decrease of the rate of appearance of ALA with RL (R2 = 0.26; P = 0.0064). Although the number of CMs was unaffected by RL, CM diameter was increased in the 30%-RL group, compared to the control group (0% RL), by 86% at 3-4 h (P = 0.065) and by 81% at 4-6 h (P = 0.0002) following administration. This increase was positively correlated with the duodenal mRNA expression of microsomal triglyceride transfer protein (Mttp; ρ= 0.63; P = 0.0052). The expression of Mttp and secretion-associated, ras-related GTPase 1 gene homolog B (Sar1b, CM secretion), carnitine palmitoyltransferase IA (Cpt1a) and acyl-coenzyme A oxidase 1 (Acox1, beta-oxidation), and fatty acid desaturase 2 (Fads2, bioconversion of ALA into long-chain n-3 PUFAs) were, respectively, 49%, 29%, 74%, 48%, and 55% higher in the 30%-RL group vs. the control group (P < 0.05).
CONCLUSIONS
In rats, RL enhanced lymphatic lipid output, as well as the rate of appearance of ALA, which may promote its subsequent bioavailability and metabolic fate.
Topics: Animals; Biological Availability; Brassica napus; Lecithins; Lipid Metabolism; Lymph; Rats; alpha-Linolenic Acid
PubMed: 32937654
DOI: 10.1093/jn/nxaa244 -
Nutrients Jan 2022The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated...
The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.
Topics: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Diet; Dietary Fats; Docosahexaenoic Acids; Female; Guinea Pigs; Linoleic Acid; Maternal Nutritional Physiological Phenomena; Phospholipids; Pregnancy; Retina; alpha-Linolenic Acid
PubMed: 35057481
DOI: 10.3390/nu14020301