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The Journal of Nutritional Biochemistry May 2021Docosahexaenoic acid (DHA) is critical for normal brain development and function. DHA is in danger of being significantly reduced in the human food supply, and the...
Docosahexaenoic acid (DHA) is critical for normal brain development and function. DHA is in danger of being significantly reduced in the human food supply, and the question of whether its metabolic precursor, the essential n-3 alpha linolenic acid (ALA) during pregnancy, can support fetal brain DHA levels for optimal neurodevelopment, is fundamental. Female mice were fed either ALA-enriched or Control diet during pregnancy and lactation. The direct effect of maternal dietary ALA on lipids was analyzed in liver, red blood cells, brain and brain vasculature, together with genes of fatty acid metabolism and transport in three-week-old offspring. The long-term effect of maternal dietary ALA on brain fatty acids and memory was studied in 19-week-old offspring. Three-week-old ALA offspring showed higher levels of n-3 fatty acids in liver, red blood cell, blood-brain barrier (BBB) vasculature and brain parenchyma, DHA enrichment in brain phospholipids and higher gene and protein expression of the DHA transporter, major facilitator superfamily domain containing 2a, compared to Controls. 19-week-old ALA offspring showed higher brain DHA levels and better memory performance than Controls. The increased brain DHA levels induced by maternal dietary ALA during pregnancy-lactation, together with the up-regulated levels of major facilitator superfamily domain containing 2a, may indicate a mode for greater DHA uptake with long-term impact on better memory in ALA offspring.
Topics: Animals; Animals, Newborn; Brain; Dietary Supplements; Docosahexaenoic Acids; Female; Memory; Mice; Mice, Inbred C57BL; Pregnancy; Weaning; alpha-Linolenic Acid
PubMed: 33545323
DOI: 10.1016/j.jnutbio.2021.108597 -
Cell Cycle (Georgetown, Tex.) May 2022Obesity is associated with elevated levels of free fatty acids (FFAs). Excessive saturated fatty acids (SFAs) exhibit significant deleterious cytotoxic effects in many...
Obesity is associated with elevated levels of free fatty acids (FFAs). Excessive saturated fatty acids (SFAs) exhibit significant deleterious cytotoxic effects in many types of cells. However, the effects of palmitic acid (PA), the most common circulating SFA, on cell cycle progression in neuronal cells have not been well-examined. The aim of this study was to examine whether PA affects the proliferation and cell cycle progression in mouse neuroblastoma Neuro-2a (N2a) cells. Our studies found that 200 µM PA significantly decreased DNA synthesis and mitotic index in N2a cells as early as 4 h following treatment. 24 h treatment with 200 µM PA significantly decreased the percentage of diploid (2 N) cells while dramatically increasing the percentage of tetraploid (4 N) cells as compared to the BSA control. Moreover, our studies found that 24 h treatment with 200 µM PA increased the percentage of binucleate cells as compared to the BSA control. Our studies also found that unsaturated fatty acids (UFAs), including linoleic acid, oleic acid, α-linolenic acid, and docosahexaenoic acid, were able to abolish PA-induced decrease of 2 N cells, increase of 4 N cells, and accumulation of binucleate cells. Taken together, these results suggest that PA may affect multiple aspects of the cell cycle progression in N2a cells, including decreased DNA synthesis, G2/M arrest, and cytokinetic failure, which could be abolished by UFAs. 4-PBA, 4-Phenylbutyric Acid; ALA, α-linolenic acid; BrdU, 5-bromo-2'-deoxyuridine; DAPI, 4',6-diamidino-2-phenylindole; ER, endoplasmic reticulum; FFA, free fatty acids; FITC, fluorescein isothiocyanate; LA, linoleic acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; N2a, Neuro-2a; NAC, N-acetyl cysteine; OA, oleic acid; PA, palmitic acid; pHH3, Phosphorylation of histone H3; PI, propidium iodide; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; UFA, unsaturated fatty acids.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cytokinesis; DNA; Fatty Acids; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; G2 Phase Cell Cycle Checkpoints; Linoleic Acids; Mice; Oleic Acids; Palmitic Acid; alpha-Linolenic Acid
PubMed: 35171079
DOI: 10.1080/15384101.2022.2040769 -
European Journal of Pharmacology Jan 2021This study examined the effect of linolenic acid on the contraction of isolated endothelium-intact and -denuded rat aorta induced by phenylephrine and its underlying...
This study examined the effect of linolenic acid on the contraction of isolated endothelium-intact and -denuded rat aorta induced by phenylephrine and its underlying mechanism. This was conducted in the presence or absence of N-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), methylene blue, and calmidazolium. The effects of linolenic acid on contraction induced by calcium chloride in calcium-free Krebs solution containing 60 mM potassium chloride were also examined. Moreover, the effect of linolenic acid on the association between intracellular calcium level ([Ca]) and tension induced by phenylephrine was examined. Finally, we examined the effects of linolenic acid on cGMP formation and endothelial nitric oxide synthase (eNOS) phosphorylation induced by phenylephrine. Linolenic acid (5 × 10 M) increased phenylephrine-induced contraction in endothelium-intact aorta (standardized mean difference [SMD] of log ED: 2.23), whereas it decreased this contraction in endothelium-denuded aorta (SMD: 1.96). L-NAME, ODQ, methylene blue, and calmidazolium increased phenylephrine-induced contraction in endothelium-intact aorta. Linolenic acid decreased contraction induced by calcium chloride in calcium-free Krebs solution containing 60 mM potassium chloride in endothelium-denuded aorta. Linolenic acid caused an increase in [Ca] (SMD at 3 × 10 M phenylephrine: 1.63) and calcium sensitivity induced by phenylephrine in endothelium-intact aorta. Conversely, linolenic acid decreased [Ca] (SMD: 0.99) induced by phenylephrine in endothelium-denuded aorta. Linolenic acid decreased cGMP formation and eNOS phosphorylation induced by phenylephrine. These results suggest that linolenic acid increases phenylephrine-induced contraction, which is attributed to linolenic acid inhibition of endothelial NO release rather than its decrease of [Ca] in vascular smooth muscle.
Topics: Animals; Aorta; Dose-Response Relationship, Drug; Drug Synergism; Human Umbilical Vein Endothelial Cells; Humans; Male; Organ Culture Techniques; Phenylephrine; Rats; Rats, Sprague-Dawley; Vasoconstriction; alpha-Linolenic Acid
PubMed: 33131719
DOI: 10.1016/j.ejphar.2020.173662 -
Nutrients Oct 2019Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets... (Review)
Review
Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. Typically, US omnivores obtain enough dietary EPA and DHA, but unless VGNs consume algal n-3 supplements, they rely on endogenous production of long-chain fatty acids. VGN diets have several possible concerns: (1) VGNs have high intakes of linoleic acid (LA) as compared to omnivore/non-vegetarian diets. (2) High intakes of LA competitively interfere with the endogenous conversion of alpha-linolenic acid (ALA) to EPA and DHA. (3) High somatic levels of LA/low ALA indicate a decreased ALA conversion to EPA and DHA. (4) Some, not all VGNs meet the Dietary Reference Intake Adequate Intake (DRI-AI) for dietary ALA and (5) VGN diets are high in fiber, which possibly interferes with fat absorption. Consequently, health professionals and Registered Dietitians/Registered Dietitian Nutritionists working with VGNs need specific essential fatty acid diet guidelines. The purpose of this review was: (1) to suggest that VGNs have a DRI-AI Special Consideration requirement for ALA and LA based on VGN dietary and biochemical indicators of status and (2) to provide suggestions to ensure that VGNs receive adequate intakes of LA and ALA.
Topics: Diet, Vegan; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Linoleic Acid; Nutritional Status; Nutritive Value; Recommended Dietary Allowances; alpha-Linolenic Acid
PubMed: 31590264
DOI: 10.3390/nu11102365 -
Clinics (Sao Paulo, Brazil) Oct 2018Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and...
OBJECTIVES
Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and molecular changes induced by the omega-3 fatty acid α-linolenic acid (ALA), which is found in linseed oil, are not fully understood. In this study, we showed a correlation between ALA and insulin resistance, inflammation and endoplasmic reticulum stress (ERS).
METHODS
We studied 40 male mice (C57/BL6) divided into 4 groups: a control (C) group, a control + omega-3/ALA (CA) group, a high-fat diet (HFD) (H) group and a high-fat diet + omega-3/ALA (HA) group. For 8 weeks, the animals in the H and HA groups were fed a high-fat (60%) diet, while the animals in the C and CA groups received regular chow. The diets of the CA and HA groups were supplemented with 10% lyophilized ALA.
RESULTS
ALA supplementation improved glucose tolerance and reduced insulin resistance, as measured by intraperitoneal glucose tolerance tests and the homeostasis model assessment for insulin resistance, respectively. In addition, ALA reduced hepatic steatosis and modified the standard fat concentration in the liver of animals fed an HFD. Dietary ALA supplementation reduced the serum levels of interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), increased the expression of important chaperones such as binding immunoglobulin protein (BIP) and heat shock protein 70 (HSP70) and reduced the expression of C/EBP-homologous protein (CHOP) and X-box binding protein 1 (XBP1) in hepatic tissues, suggesting an ERS adaptation in response to ALA supplementation.
CONCLUSIONS
Dietary ALA supplementation is effective in preventing hepatic steatosis; is associated with a reduction in insulin resistance, inflammation and ERS; and represents an alternative for improving liver function and obtaining metabolic benefits.
Topics: Animals; Diet, High-Fat; Dietary Supplements; Endoplasmic Reticulum Stress; Fatty Acids, Omega-3; Fatty Liver; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; alpha-Linolenic Acid
PubMed: 30379219
DOI: 10.6061/clinics/2018/e150 -
Food Chemistry Mar 2023Nanoliposome encapsulation combined with carboxymethyl chitosan (CMCS) surface decoration was employed to improve physicochemical stability and oral bioavailability of...
Nanoliposome encapsulation combined with carboxymethyl chitosan (CMCS) surface decoration was employed to improve physicochemical stability and oral bioavailability of alpha-linolenic acid (ALA). Different nanoliposome systems including ALA-loaded nanoliposomes (ALA-NLs) and CMCS-coated ALA-NLs (CMCS-ALA-NLs) were characterized through dynamic light scattering, transmission electron microscope, Fourier transform infrared spectroscopy and differential scanning calorimetry. The results showed that CMCS-ALA-NLs had good encapsulation efficiency of 79% and layer formation with nanosized spherical carrier. The physicochemical stability of CMCS-ALA-NLs was better than that of ALA-NLs. CMCS-ALA-NLs were able to regulate the release of ALA in a simulated gastrointestinal environment. In vivo testing found that ALA concentration of CMCS-ALA-NLs had an area under the curve of 1.32, which was 1.28 times higher than that of ALA-NLs and 2 times higher than that of ALA-emulsion. The absorption of ALA was improved by CMCS-ALA-NLs. It suggested that CMCS-coated nanoliposomes should be an available delivery strategy for transporting ALA.
Topics: alpha-Linolenic Acid; Biological Availability; Chemical Phenomena; Chitosan
PubMed: 36265276
DOI: 10.1016/j.foodchem.2022.134526 -
BioMed Research International 2015Alpha-linolenic acid (ALA) is plant-based essential omega-3 polyunsaturated fatty acids that must be obtained through the diet. This could explain in part why the severe... (Review)
Review
Alpha-linolenic acid (ALA) is plant-based essential omega-3 polyunsaturated fatty acids that must be obtained through the diet. This could explain in part why the severe deficiency in omega-3 intake pointed by numerous epidemiologic studies may increase the brain's vulnerability representing an important risk factor in the development and/or deterioration of certain cardio- and neuropathologies. The roles of ALA in neurological disorders remain unclear, especially in stroke that is a leading cause of death. We and others have identified ALA as a potential nutraceutical to protect the brain from stroke, characterized by its pleiotropic effects in neuroprotection, vasodilation of brain arteries, and neuroplasticity. This review highlights how chronic administration of ALA protects against rodent models of hypoxic-ischemic injury and exerts an anti-depressant-like activity, effects that likely involve multiple mechanisms in brain, and may be applied in stroke prevention. One major effect may be through an increase in mature brain-derived neurotrophic factor (BDNF), a widely expressed protein in brain that plays critical roles in neuronal maintenance, and learning and memory. Understanding the precise roles of ALA in neurological disorders will provide the underpinnings for the development of new therapies for patients and families who could be devastated by these disorders.
Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Fatty Acids, Omega-3; Humans; Neuroprotective Agents; Stroke; alpha-Linolenic Acid
PubMed: 25789320
DOI: 10.1155/2015/519830 -
Meat Science Oct 2016Fresh and processed meats provide high biological value proteins and important micronutrients. On the other hand, a working group of IARC recently classified processed... (Review)
Review
Fresh and processed meats provide high biological value proteins and important micronutrients. On the other hand, a working group of IARC recently classified processed meat as 'carcinogenic to humans' and red meat as 'probably carcinogenic to humans' for colorectal cancer, appealing to critically consider the future role of meat in a healthy diet. This manuscript first evaluates the contribution of meat consumption to the supply of important micronutrients in the human food chain, and the extent to which this can be improved by primary production strategies, and impacts on human health. Secondly, the IARC hazard analysis of the carcinogenicity of red and processed meat consumption is discussed, arguing that having more insight in the mechanisms of the association offers opportunities for mitigation. It is advocated that the benefits and risks associated with red and processed meat consumption should not necessarily cause dilemmas, if these meats are consumed in moderate amounts as part of balanced diets.
Topics: Adipose Tissue; Animals; Colorectal Neoplasms; Diet, Healthy; Energy Intake; Fatty Acids, Omega-3; Health Promotion; Humans; Meat Products; Micronutrients; Nutritional Status; Randomized Controlled Trials as Topic; Red Meat; Risk Assessment; alpha-Linolenic Acid
PubMed: 27107745
DOI: 10.1016/j.meatsci.2016.04.008 -
International Immunopharmacology Feb 2022Excessive reactions to allergens can induce systemic, life-threatening physiological dysfunction (anaphylaxis) in humans. The surface of mast cells expresses...
Excessive reactions to allergens can induce systemic, life-threatening physiological dysfunction (anaphylaxis) in humans. The surface of mast cells expresses high-affinity IgE receptors that play a vital role during anaphylaxis. Alpha-linolenic acid (ALA) is an essential non-toxic fatty acid in humans. Since it has been reported having potential to regulate pro-inflammatory reactions, we postulated that ALA could inhibit anaphylaxis by down-regulating Lyn kinase phosphorylation. We found that local and systematic inflammation induced by albumin from chicken egg white (OVA) were attenuated by ALA in vivo. Furthermore, ALA inhibited IgE-mediated Ca mobilization, degranulation, and cytokine release in Laboratory of Allergic Disease 2 (LAD2) cells. The western blot results showed that ALA down-regulate the FcεRI/Lyn/Syk signaling pathway by suppressing Lyn kinase activity. Therefore, ALA could serve as a therapeutic drug candidate for preventing IgE-mediated anaphylaxis.
Topics: Allergens; Anaphylaxis; Animals; Cell Degranulation; Humans; Immunoglobulin E; Mast Cells; Passive Cutaneous Anaphylaxis; Phosphorylation; Protein Kinase Inhibitors; Receptors, IgE; Signal Transduction; Syk Kinase; alpha-Linolenic Acid; src-Family Kinases
PubMed: 34929479
DOI: 10.1016/j.intimp.2021.108449 -
Life Sciences Dec 2022Evolving type 2 diabetes (T2D) may influence locomotion and affective state, promoting metabolic dysfunction. We examined behaviour and neurobiology in a model of T2D,...
AIM
Evolving type 2 diabetes (T2D) may influence locomotion and affective state, promoting metabolic dysfunction. We examined behaviour and neurobiology in a model of T2D, testing for benefits with dietary n-3 polyunsaturated fatty acid (PUFA).
METHODS
Male C57Bl/6 mice received vehicle or 75 mg/kg streptozotocin (STZ) and 21 wks of control or Western diets (43 % fat, 40 % carbohydrate, 17 % protein). Sub-sets received dietary α-linolenic acid (ALA; 10 % of fat intake) for 6 wks. Behaviour was examined via open field and sucrose preference tests, and hippocampal and frontal cortex (FC) leptin and dopamine levels and inflammatory signalling assessed.
KEY FINDINGS
T2D mice exhibited weight gain (+15 %), hyperglycemia (+35 %), hyperinsulinemia (+60 %) and insulin-resistance (+80 % higher HOMA-IR), together with anxiety-like behaviour (without anhedonia) that appeared independent of body weight and glycemic status. Cortical leptin declined whereas receptor mRNA increased. Supplementation with ALA did not influence metabolic state, while enhancing locomotion and reducing anxiety-like behaviours in healthy but not T2D mice. Hippocampal dopamine was selectively increased by ALA in T2D mice, with a trend to reduced circulating leptin in both groups. Across all groups, anxiety-like behaviour was associated with declining cortical and hippocampal leptin levels and increasing receptor mRNA, while declining dopamine levels were accompanied by decreased dopamine/serotonin receptor transcripts.
SIGNIFICANCE
Chronic T2D induced anxiogenesis in mice appears to be independent of metabolic homeostasis but linked to central leptin-resistance, together with disturbed dopamine and serotonin signalling. Despite anxiolytic effects of ALA in healthy mice, no metabolic or behavioural benefits were evident in T2D.
Topics: Male; Mice; Animals; alpha-Linolenic Acid; Leptin; Diabetes Mellitus, Type 2; Diabetes Mellitus, Experimental; Neurobiology; Dopamine; Fatty Acids; Diet, Western; RNA, Messenger
PubMed: 36349604
DOI: 10.1016/j.lfs.2022.121137