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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 -
Molecules (Basel, Switzerland) Apr 2020Oxidized low-density lipoprotein (Ox-LDL) is known to be highly atherogenic. Thus, decreasing the blood levels of Ox-LDL through dietary means is an important approach...
Oxidized low-density lipoprotein (Ox-LDL) is known to be highly atherogenic. Thus, decreasing the blood levels of Ox-LDL through dietary means is an important approach to reduce cardiovascular events in high-risk individuals. In this randomized placebo-controlled human interventional trial, we aimed to evaluate whether leaf powder (PLP) ameliorates Ox-LDL and home blood pressure, along with its biological antioxidant potential. Healthy Japanese volunteers aged 30-60 years ( = 60) were randomized to PLP and placebo groups. The PLP group consumed PLP dried using a microwave under reduced pressure, and the placebo group consumed pectin fiber daily for 6 months. Home blood pressure, serum biochemical parameters, and fatty acid profiles of erythrocyte plasma membranes were analyzed. Plasma Ox-LDL levels significantly decreased in the PLP group but not in the placebo group. Mean changes in the biological antioxidant potential and alpha-linolenic acid levels in the erythrocyte plasma membrane were significantly increased in the PLP group than in the placebo group. In subjects with prehypertension (systolic blood pressure [SBP] ³ 120 mmHg), the mean reduction in morning or nocturnal SBP was significantly greater in the PLP group than in the placebo group. Thus, PLP intake may be an effective intervention to prevent cardiovascular diseases.
Topics: Adult; Biomarkers; Blood Pressure; Body Composition; Dietary Supplements; Drugs, Chinese Herbal; Erythrocyte Membrane; Fatty Acids; Female; Humans; Japan; Lipid Metabolism; Lipoproteins, LDL; Male; Middle Aged; Perilla frutescens; Plant Leaves; Powders; alpha-Linolenic Acid
PubMed: 32365849
DOI: 10.3390/molecules25092099 -
The Journal of Physiology Jul 2017α-linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia-related cardiovascular derangements, however, there is a paucity of information pertaining...
KEY POINTS
α-linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia-related cardiovascular derangements, however, there is a paucity of information pertaining to their mechanisms of action when combined. We investigated both the independent and combined effects of exercise training and ALA consumption in obese Zucker rats, aiming to determine the potential for additive improvements in cardiovascular function. ALA and exercise training independently improved cardiac output, end-diastolic volume, left ventricular fibrosis and mean blood pressure following a 4 week intervention. Combining ALA and endurance exercise yielded greater improvements in these parameters, independent of changes in markers of oxidative stress or endogenous anti-oxidants. We postulate that divergent mechanisms of action may explain these changes: ALA increases peripheral vasodilation, and exercise training stimulates angiogenesis.
ABSTRACT
Although α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4 week intervention, although the independent and combined effects of ALA and exercise reduced (P < 0.05) the serum free/esterified cholesterol ratio, only the ALA supplemented-exercise trained animals displayed a reduction in the content of both serum free and esterified cholesterol. Moreover, although ALA and endurance training individually increased cardiac output, stroke volume and end-diastolic volume, as well as reduced left ventricle fibrosis, mean blood pressure and total peripheral resistance, these responses were all greater following the combined intervention (ALA supplemented-exercise trained). These effects occurred independent of changes in oxidative phosphorylation proteins, markers of oxidative stress or endogenous anti-oxidant capacity. We propose that the beneficial effects of a combined intervention occur as a result of divergent mechanisms of action elicited by ALA and endurance exercise because only exercise training increased the capillary content in the left ventricle and skeletal muscle, and tended to decrease protein carbonylation in the left ventricle (P = 0.06). Taken together, our data indicate that combining ALA and endurance exercise provides additional improvements in cardiovascular disease risk reduction compared to singular interventions in the obese Zucker rat.
Topics: Animals; Blood Pressure; Cardiovascular Diseases; Cholesterol; Diastole; Exercise Therapy; Heart Rate; Male; Obesity; Physical Conditioning, Animal; Rats; Rats, Zucker; alpha-Linolenic Acid
PubMed: 28345766
DOI: 10.1113/JP274036 -
The American Journal of Clinical... Mar 2011
Topics: Adult; Diet; Fatty Acids, Omega-3; Female; Humans; Male; Publishing; Sex Characteristics; alpha-Linolenic Acid
PubMed: 21191139
DOI: 10.3945/ajcn.110.008169 -
Molecular Neurobiology Jan 2018Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while...
Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while most patients recover completely from mild TBI (mTBI) about 10% result in persistent symptoms and some result in lifelong disability. Anxiety disorders are the second most common diagnosis post-TBI. Of note, TBI-induced anxiety disorders are difficult to treat and remain a chronic condition suggesting that new therapies are needed. Previous work from our laboratory demonstrated that a mild TBI induced an anxiety-like phenotype, a key feature of the human condition, associated with loss of GABAergic interneurons and hyperexcitability in the basolateral amygdala (BLA) in rodents 7 and 30 days after a controlled cortical impact (CCI) injury. We now confirm that animals display significantly increased anxiety-like behavior 30 days after CCI. The anxiety-like behavior was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABA-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the BLA. Significantly, subchronic treatment with alpha-linolenic acid (ALA) after CCI prevents the development of anxiety-like behavior, the loss of GABAergic interneurons, hyperexcitability in the BLA and reduces the impact injury. Taken together, administration of ALA after CCI is a potent therapy against the neuropathology and pathophysiological effects of mTBI in the BLA.
Topics: Animals; Anxiety; Brain Injuries, Traumatic; Contusions; Inhibitory Postsynaptic Potentials; Male; Rats; Rats, Sprague-Dawley; Treatment Outcome; alpha-Linolenic Acid
PubMed: 28844093
DOI: 10.1007/s12035-017-0732-y -
World Review of Nutrition and Dietetics 2022
Review
Topics: Diet; Dietary Fats; Fatty Acids; Humans; Linoleic Acid; alpha-Linolenic Acid
PubMed: 35240621
DOI: 10.1159/000516721 -
Haematologica Jun 2020Platelet adhesion to the sub-endothelial matrix and damaged endothelium occurs through a multi-step process mediated in the initial phase by glycoprotein Ib binding to...
Platelet adhesion to the sub-endothelial matrix and damaged endothelium occurs through a multi-step process mediated in the initial phase by glycoprotein Ib binding to von Willebrand factor (vWF), which leads to the subsequent formation of a platelet plug. The plant-derived ω-3 fatty acid α-linolenic acid is an abundant alternative to fish-derived n-3 fatty acids and has anti-inflammatory and antithrombotic properties. In this study, we investigated the impact of α-linolenic acid on human platelet binding to vWF under high-shear flow conditions (mimicking blood flow in stenosed arteries). Pre-incubation of fresh human blood from healthy donors with α-linolenic acid at dietary relevant concentrations reduced platelet binding and rolling on vWF-coated microchannels at a shear rate of 100 dyn/cm Depletion of membrane cholesterol by incubation of platelet-rich plasma with methyl-β cyclodextrin abrogated platelet rolling on vWF. Analysis of glycoprotein Ib by applying cryo-electron tomography to intact platelets revealed local clusters of glycoprotein Ib complexes upon exposure to shear force: the formation of these complexes could be prevented by treatment with α-linolenic acid. This study provides novel findings on the rapid local rearrangement of glycoprotein Ib complexes in response to high-shear flow and highlights the mechanism of inhibition of platelet binding to and rolling on vWF by α-linolenic acid.
Topics: Animals; Blood Platelets; Cluster Analysis; Electron Microscope Tomography; Humans; Platelet Glycoprotein GPIb-IX Complex; alpha-Linolenic Acid; von Willebrand Factor
PubMed: 31439672
DOI: 10.3324/haematol.2019.220988 -
Biomeditsinskaia Khimiia 2004Flaxseed oil is the most abundant plant source of omega-3 fatty acid, alpha-linolenic acid omega-3. This review focuses on the biological effects of dietary... (Review)
Review
Flaxseed oil is the most abundant plant source of omega-3 fatty acid, alpha-linolenic acid omega-3. This review focuses on the biological effects of dietary alpha-linolenic acid (ALA) compared with long-chain omega-3 derivatives. ALA is not equivalent in its biological effects to the long-chain omega-3 fatty acids found in marine fish oils. However, ALA is metabolized to eicosapentaenoic acid, which may replace arachidonic acid in membrane phospholipides. Ingestion of flaxseed oil may alter the generation of eicosanoids, procoagulant activity and other membrane-dependent responses and exert antiallergic, antiatherosclerotic, antiarrhythmic effects. Beneficial effects of flaxseed oil have been shown in prevention and management of cardiovascular disease.
Topics: Animals; Cardiovascular Diseases; Cytokines; Eicosanoids; Humans; Linseed Oil; alpha-Linolenic Acid
PubMed: 15108624
DOI: No ID Found -
The Journal of Nutrition Aug 2015Associations of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) plus decosahexaenoic acid (DHA), and total omega-3 (n-3) fatty acid (FA) intakes with abdominal...
BACKGROUND
Associations of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) plus decosahexaenoic acid (DHA), and total omega-3 (n-3) fatty acid (FA) intakes with abdominal aortic calcification (AAC) are not well understood.
OBJECTIVE
This study explored the associations between baseline and long-term changes in ω-3 FA consumption and AAC severity among community-dwelling older men and women.
METHODS
The present study used a subset of the Melbourne Collaborative Cohort Study in which participants were interviewed in 1990-1994 and again in 2010-2011. Dietary intake was evaluated at both baseline and follow-up with use of food-frequency questionnaires. AAC severity was assessed by both lateral thoraco-lumbar radiography and dual-energy X-ray absorptiometry (DXA) at follow-up.
RESULTS
A total of 312 participants aged 45-64 y old at baseline were followed for a duration of (mean ± SD) 18 ± 1 y. Baseline energy-adjusted ALA intake tended to be inversely associated with AAC severity by radiography [OR (95% CI) for tertile 3 vs. tertile 1: 0.49 (0.23, 1.02), P-trend: 0.06] and was inversely associated with AAC severity by DXA [OR (95% CI) for tertile 3 vs. tertile 1: 0.37 (0.16, 0.83)] in women, after adjustment for confounders. Women in the third tertile of total ω-3 FA intake had significantly lower AAC severity by radiography [OR (95% CI): 0.33 (0.16, 0.71)] and DXA [OR (95% CI): 0.27 (0.12, 0.62)] than those in the first tertile. Changes in tertile of ω-3 FA intake over 18 y were not found to be associated with AAC severity in either men or women.
CONCLUSION
The results of our study suggest that dietary ALA and total ω-3 FA intakes are both important predictors of the development of AAC in older women, but not in older men.
Topics: Aged; Aging; Aorta, Abdominal; Calcinosis; Diet; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Female; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Risk Factors; Sex Factors; alpha-Linolenic Acid
PubMed: 26041673
DOI: 10.3945/jn.115.211789 -
Food and Chemical Toxicology : An... Aug 2017Alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil is an edible oil enriched with DAG (>80%) and ALA (>50%). The present study investigated whether ALA-DAG oil...
Alpha-linolenic acid-enriched diacylglycerol oil does not promote tumor development in tongue and gastrointestinal tract tissues in a medium-term multi-organ carcinogenesis bioassay using male F344 rat.
Alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil is an edible oil enriched with DAG (>80%) and ALA (>50%). The present study investigated whether ALA-DAG oil promotes tumorigenesis in the tongue and gastrointestinal tract, using a rat medium-term multi-organ carcinogenesis bioassay model. Rats were treated with five genotoxic carcinogens to induce multi-organ tumorigenesis until week 4, and from 1 week after withdrawal, fed a semi-synthetic diet (AIN-93G) containing ALA-DAG oil at concentrations of 0, 13,750, 27,500, and 55,000 ppm. Rats fed AIN-93G containing 55,000 ppm ALA-triacylglycerol or a standard basal diet served as reference and negative control groups, respectively. Animals were euthanized at week 30. ALA-DAG oil was shown to have no effects on survival, general condition, body weight, food consumption, or organ weight. More discolored spots were observed in the stomachs of the 13,750- and 55,000-ppm ALA-DAG groups than in those of the control groups; however, there were no differences in the frequency of histopathological findings across groups. There were no meaningful increases in the incidence of pre-neoplastic and neoplastic lesions in the tongue and gastrointestinal tract among the groups. We therefore conclude that ALA-DAG oil does not promote tumor development in the digestive system.
Topics: Animals; Biological Assay; Carcinogenicity Tests; Diglycerides; Gastrointestinal Tract; Male; Rats; Rats, Inbred F344; Tongue; alpha-Linolenic Acid
PubMed: 28465188
DOI: 10.1016/j.fct.2017.04.040