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Progress in Lipid Research Jul 2015Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate... (Review)
Review
Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats.
Topics: Animals; Biosynthetic Pathways; Brain; Diet; Docosahexaenoic Acids; Humans; alpha-Linolenic Acid
PubMed: 25920364
DOI: 10.1016/j.plipres.2015.04.002 -
Scientific Reports Mar 2023Metabolic disorders are often linked to alterations in insulin signaling. Omega-3 (n-3) fatty acids modulate immunometabolic responses; thus, we examined the effects of...
Metabolic disorders are often linked to alterations in insulin signaling. Omega-3 (n-3) fatty acids modulate immunometabolic responses; thus, we examined the effects of peripartum n-3 on systemic and adipose tissue (AT)-specific insulin sensitivity, immune function, and the endocannabinoid system (ECS) in dairy cows. Cows were supplemented peripartum with saturated fat (CTL) or flaxseed supplement rich in alpha-linolenic acid (ALA). Blood immunometabolic biomarkers were examined, and at 5-8 d postpartum (PP), an intravenous glucose-tolerance-test (GTT) and AT biopsies were performed. Insulin sensitivity in AT was assessed by phosphoproteomics and proteomics. Peripartum n-3 reduced the plasma concentrations of Interleukin-6 (IL-6) and IL-17α, lowered the percentage of white blood cells PP, and reduced inflammatory proteins in AT. Systemic insulin sensitivity was higher in ALA than in CTL. In AT, the top canonical pathways, according to the differential phosphoproteome in ALA, were protein-kinase-A signaling and insulin-receptor signaling; network analysis and immunoblots validated the lower phosphorylation of protein kinase B (Akt), and lower abundance of insulin receptor, together suggesting reduced insulin sensitivity in ALA AT. The n-3 reduced the plasma concentrations of ECS-associated ligands, and lowered the abundances of cannabinoid-1-receptor and monoglycerol-lipase in peripheral blood mononuclear cells PP. Peripartum ALA supplementation in dairy cows improved systemic insulin sensitivity and immune function, reduced ECS components, and had tissue-specific effects on insulin-sensitivity in AT, possibly counter-balancing the systemic responses.
Topics: Female; Cattle; Animals; Insulin Resistance; Endocannabinoids; alpha-Linolenic Acid; Leukocytes, Mononuclear; Adipose Tissue; Insulin; Inflammation; Lactation; Diet
PubMed: 37002295
DOI: 10.1038/s41598-023-32433-7 -
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 Nov 2022Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing...
Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.
Topics: Humans; Alzheimer Disease; Blood-Brain Barrier; alpha-Linolenic Acid; Brain; Apolipoprotein E4
PubMed: 36501121
DOI: 10.3390/nu14235091 -
Food & Function Jul 2022Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also...
Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also provides substantial amounts of linoleic acid (LA). This study aimed to test the bioavailability of the oil derived from basil seeds and its effects on different physiological parameters using 7-15% dietary inclusion levels. Furthermore, the assimilation of LA and ALA and their transformation in long-chain polyunsaturated fatty acids (LC-PUFAs) have been studied. Digestive utilization of total fat from basil seed oil (BSO) was high and similar to that of olive oil used as a control. Consumption of BSO resulted in increased LA and ALA levels of the plasma, liver, and erythrocyte membrane. In addition, the transformation of LA to arachidonic acid (ARA) was decreased by the high dietary intake of ALA which redirected the pathway of the Δ-6 desaturase enzyme towards the transformation of ALA into eicosapentaenoic acid (EPA). No alterations of hematological and plasma biochemical parameters were found for the 7 and 10% dietary inclusion levels of BSO, whereas a decrease in the platelet count and an increase in total- and HDL-cholesterol as well as plasma alkaline phosphatase (ALP) were found for a 15% BSO dose. In conclusion, BSO is a good source of ALA to be transformed into EPA and decrease the precursor of the pro-inflammatory molecule ARA. This effect on the levels of EPA in different tissues offers potential for its use as a dietary supplement, novel functional food, or a constituent of nutraceutical formulations to treat different pathologies.
Topics: Animals; Arachidonic Acid; Biological Availability; Biotransformation; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Linoleic Acid; Models, Theoretical; Ocimum basilicum; Plant Oils; Rats; Seeds; alpha-Linolenic Acid
PubMed: 35731538
DOI: 10.1039/d2fo00672c -
Bioscience, Biotechnology, and... Jun 2020Antibacterial activities against and were found in an ethanol fraction of tempe, an Indonesian fermented soybean produced using . The ethanol fraction contained free...
Antibacterial activities against and were found in an ethanol fraction of tempe, an Indonesian fermented soybean produced using . The ethanol fraction contained free fatty acids, monoglycerides, and fatty acid ethyl esters. Among these substances, linoleic acid and α-linolenic acid exhibited antibacterial activities against and , whereas 1-monolinolenin and 2-monolinolenin exhibited antibacterial activity against . The other free fatty acids, 1-monoolein, monolinoleins, ethyl linoleate, and ethyl linolenate did not exhibit bactericidal activities. These results revealed that produced the long-chain polyunsaturated fatty acids and monolinolenins as antibacterial substances against the Gram-positive bacteria during the fungal growth and fermentation of heat-processed soybean.
Topics: Anti-Bacterial Agents; Bacillus subtilis; Ethanol; Fatty Acids, Nonesterified; Fermentation; Food Microbiology; Hot Temperature; Microbial Sensitivity Tests; Rhizopus; Soy Foods; Glycine max; Staphylococcus aureus; alpha-Linolenic Acid
PubMed: 32089087
DOI: 10.1080/09168451.2020.1731299 -
Methods in Molecular Biology (Clifton,... 2024Neuroinflammation is the brain condition that occurs due to the hyper-activation of brain's immune cells and microglia, over the stimulation of extracellular aggregated...
Neuroinflammation is the brain condition that occurs due to the hyper-activation of brain's immune cells and microglia, over the stimulation of extracellular aggregated proteins such as amyloid plaques and by extracellular Tau as well. The phenotypic changes of microglia from inflammatory to anti-inflammatory can be triggered by many factors, which also includes dietary fatty acids. The classes of omega-3 fatty acids are the majorly responsible in maintaining the anti-inflammatory phenotype of microglia. The enhanced phagocytic ability of microglia might induce the clearance of extracellular aggregated proteins, such as amyloid beta and Tau. In this study, we emphasized on the effect of α-linolenic acid (ALA) on the activation of microglia and internalization of the extracellular Tau seed in microglia.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; alpha-Linolenic Acid; Microglia; Anti-Inflammatory Agents; tau Proteins
PubMed: 38512683
DOI: 10.1007/978-1-0716-3629-9_26 -
The Journal of Nutrition Mar 2021Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins.
OBJECTIVES
Time course and sex differences of plasma oxylipins in response to ALA- compared with DHA-rich supplements were examined.
METHODS
Healthy men and women, aged 19-34 y and BMI 18-28 kg/m2, were provided with capsules containing ∼4 g/d of ALA or DHA in a randomized double-blind crossover study with >6-wk wash-in and wash-out phases. Plasma PUFA and oxylipin (primary outcome) concentrations at days 0, 1, 3, 7, 14, and 28 of supplementation were analyzed by GC and HPLC-MS/MS, respectively. Sex differences, supplementation and time effects, and days to plateau were analyzed.
RESULTS
ALA supplementation doubled ALA concentrations, but had no effects on ALA oxylipins after 28 d, whereas DHA supplementation tripled both DHA and its oxylipins. Increases in DHA oxylipins were detected as early as day 1, and a plateau was reached by days 5-7 for 11 of 12 individual DHA oxylipins and for total DHA oxylipins. Nine individual DHA oxylipins reached a plateau in females with DHA supplementation, compared with only 4 in males. A similar time course and sex difference pattern occurred with EPA and its oxylipins with DHA supplementation. DHA compared with ALA supplementation also resulted in higher concentrations of 4 individual arachidonic acids, 1 linoleic acid, and 1 dihomo-γ-linolenic acid oxylipin, despite not increasing the concentrations of these fatty acids, further demonstrating that oxylipins do not always reflect their precursor PUFA.
CONCLUSIONS
DHA compared with a similar dose of ALA has greater effects on both n-3 and n-6 oxylipins in young, healthy adults, with differences in response to DHA supplementation occurring earlier and being greater in females. These findings can help explain differences in dietary effects of ALA and DHA.This study was registered at clinicaltrials.gov as NCT02317588.
Topics: Adult; Cross-Over Studies; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Humans; Male; Oxylipins; Sex Factors; Time Factors; Young Adult; alpha-Linolenic Acid
PubMed: 33097936
DOI: 10.1093/jn/nxaa294 -
Cell Death & Disease Feb 2020Although dietary α-linolenic acid (ALA) or linolenic acid (LA) intake was reported to be epidemiologically associated with a lower prevalence of hypertension, recent...
Although dietary α-linolenic acid (ALA) or linolenic acid (LA) intake was reported to be epidemiologically associated with a lower prevalence of hypertension, recent clinical trials have yielded conflicting results. Comparable experimental evidence for the roles of these two different fatty acids is still lacking and the underlying mechanisms need to be further elucidated. Our data showed that ALA but not LA supplementation alleviated systolic blood pressure elevation and improved ACh-induced, endothelium-dependent vasodilation in both spontaneously hypertensive rats (SHRs) and AngII-induced hypertensive mice. In addition, SHRs displayed reduced vascular Sirtuin 3 (SIRT3) expression, subsequent superoxide dismutase 2 (SOD2) hyperacetylation and mitochondrial ROS overproduction, all of which were ameliorated by ALA but not LA supplementation. In primary cultured endothelial cells, ALA treatment directly inhibited SIRT3 reduction, SOD2 hyperacetylation, mitochondrial ROS overproduction and alleviated autophagic flux impairment induced by AngII plus TNFα treatment. However, these beneficial effects of ALA were completely blocked by silencing SIRT3. Restoration of autophagic flux by rapamycin also inhibited mitochondrial ROS overproduction in endothelial cells exposed to AngII plus TNFα. More interestingly, SIRT3 KO mice developed severe hypertension in response to a low dose of AngII infusion, while ALA supplementation lost its anti-hypertensive and endothelium-protective effects on these mice. Our findings suggest that ALA but not LA supplementation improves endothelial dysfunction and diminishes experimental hypertension by rescuing SIRT3 impairment to restore autophagic flux and mitochondrial redox balance in endothelial cells.
Topics: Acetylation; Angiotensin II; Animals; Antihypertensive Agents; Autophagy; Cells, Cultured; Dietary Supplements; Endothelial Cells; Hypertension; Mice; Mitochondria; Oxidation-Reduction; Rats; Reactive Oxygen Species; Sirtuin 3; Superoxide Dismutase; Tumor Necrosis Factor-alpha; alpha-Linolenic Acid
PubMed: 32015327
DOI: 10.1038/s41419-020-2277-7 -
International Journal of Molecular... Aug 2018Jasmonic acid (JA) and its related derivatives are ubiquitously occurring compounds of land plants acting in numerous stress responses and development. Recent studies... (Review)
Review
Jasmonic acid (JA) and its related derivatives are ubiquitously occurring compounds of land plants acting in numerous stress responses and development. Recent studies on evolution of JA and other oxylipins indicated conserved biosynthesis. JA formation is initiated by oxygenation of α-linolenic acid (α-LeA, 18:3) or 16:3 fatty acid of chloroplast membranes leading to 12-oxo-phytodienoic acid (OPDA) as intermediate compound, but in and , OPDA and some of its derivatives are final products active in a conserved signaling pathway. JA formation and its metabolic conversion take place in chloroplasts, peroxisomes and cytosol, respectively. Metabolites of JA are formed in 12 different pathways leading to active, inactive and partially active compounds. The isoleucine conjugate of JA (JA-Ile) is the ligand of the receptor component COI1 in vascular plants, whereas in the bryophyte COI1 perceives an OPDA derivative indicating its functionally conserved activity. JA-induced gene expressions in the numerous biotic and abiotic stress responses and development are initiated in a well-studied complex regulation by homeostasis of transcription factors functioning as repressors and activators.
Topics: Bryopsida; Chloroplasts; Cyclopentanes; Fatty Acids; Fatty Acids, Unsaturated; Marchantia; Metabolic Networks and Pathways; Oxylipins; Peroxisomes; Species Specificity; alpha-Linolenic Acid
PubMed: 30150593
DOI: 10.3390/ijms19092539