-
The Journal of Nutritional Biochemistry Sep 2022Apoptosis is a feature of progressions steatosis to nonalcoholic steatohepatitis (NASH) and can be explained by endoplasmic reticulum stress (ERS). The present study...
Plant sterol ester of α-linolenic acid improved non-alcoholic fatty liver disease by attenuating endoplasmic reticulum stress-triggered apoptosis via activation of the AMPK.
Apoptosis is a feature of progressions steatosis to nonalcoholic steatohepatitis (NASH) and can be explained by endoplasmic reticulum stress (ERS). The present study aimed to investigate the protective effects of plant sterol ester of α-linolenic acid (PS-ALA) on ERS-triggered apoptosis in high fat diet-fed mice and oleic acid-induced hepatocytes, and further explore the underlying mechanisms. Our results showed that PS-ALA improved Non-alcoholic fatty liver disease (NAFLD) in both in vivo and in vitro models. Moreover, PS-ALA treatment can attenuate ERS and associated apoptosis via inhibiting IRE1α/TRAF2/JNK signal pathway. Furthermore, we found that the protective effect of PS-ALA on ERS-triggered apoptosis was mediated by activation of AMP-activated protein kinase (AMPK) as pretreatment with Compound C, an AMPK inhibitor, abolished the anti-apoptotic effect of PS-ALA. Taken together, our results illustrate that PS-ALA attenuating ERS-mediated apoptosis via activating AMPK, which provided new insights into the protective effect of PS-ALA in NAFLD.
Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Endoplasmic Reticulum Stress; Endoribonucleases; Esters; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phytosterols; Protein Serine-Threonine Kinases; alpha-Linolenic Acid
PubMed: 35660097
DOI: 10.1016/j.jnutbio.2022.109072 -
Journal of Animal Physiology and Animal... Apr 2014The effect of α-linolenic acid from a flaxseed (FLX)-enriched diet on plasma lipid and fatty acid metabolism and possible atherosclerosis risk factors was studied in... (Randomized Controlled Trial)
Randomized Controlled Trial
Conversion of α-linolenic acid to long-chain omega-3 fatty acid derivatives and alterations of HDL density subfractions and plasma lipids with dietary polyunsaturated fatty acids in Monk parrots (Myiopsitta monachus).
The effect of α-linolenic acid from a flaxseed (FLX)-enriched diet on plasma lipid and fatty acid metabolism and possible atherosclerosis risk factors was studied in Monk parrots (Myiopsitta monachus). Twenty-four Monk parrots were randomly assigned to diets containing either 10% ground SUNs or 10% ground FLXs. Feed intake was calculated daily. Blood samples, body condition scores and body weights were obtained at -5 weeks, day 0, 7, 14, 28, 42 and 70. Plasma samples were analysed for total cholesterol, free cholesterol, triacylglycerols and lipoproteins. Phospholipid subfraction fatty acid profiles were determined. By day 70, the FLX group had significantly higher plasma phospholipid fatty acids including 18:3n-3 (α-linolenic acid), 20:5n-3 (eicosapentaenoic acid) and 22:6n-3 (docosahexaenoic acid). The sunflower group had significantly higher plasma phospholipid levels of 20:4n-6 (arachidonic acid). By day 70, the high-density lipoprotein (HDL) peak shifted resulting in significantly different HDL peak densities between the two experimental groups (1.097 g/ml FLX group and 1.095 g/ml SUN group, p = 0.028). The plasma fatty acid results indicate that Monk parrots can readily convert α-linolenic acid to the long-chain omega-3 derivatives including docosahexaenoic acid and reduce 20:4n-6 accumulation in plasma phospholipids. The reason for a shift in the HDL peak density is unknown at this time.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Cholesterol, HDL; Diet; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Lipids; Parrots; alpha-Linolenic Acid
PubMed: 23600588
DOI: 10.1111/jpn.12076 -
International Journal of Food Sciences... Aug 2017The pro- or anti-inflammatory bioactivity of dietary essential linoleic acid (LA) and alpha-linolenic acid (ALA) is mainly attributed to rate-limiting delta-6 desaturase...
The pro- or anti-inflammatory bioactivity of dietary essential linoleic acid (LA) and alpha-linolenic acid (ALA) is mainly attributed to rate-limiting delta-6 desaturase (D6D) activity. The aim of this study was to analyze mechanisms of D6D-substrates ALA, LA and D6D-product gamma-linolenic acid (GLA) under D6D-deficient conditions. Fatty acid profiles (GC-MS), D6D gene expression (real-time RT-PCR) and NFκB activity (luciferase assay) were assessed in HEK293 cells. FADS2 gene expression was approved being marginal. Incubation with ALA or LA did not increase D6D products but their elongase products C20:3n-3 and C20:2n-6. Bypassing the D6D, GLA elevated C20:3n-6 and C20:4n-6. LA significantly increased (+18% at 60 μM; p < .001), ALA reduced (-32% at 100 μM; p < .001) and GLA did not specifically change NFκB activity. Our data indicate that D6D might not be essential for the distinct effects of LA and ALA on NFκB activity.
Topics: Fatty Acid Desaturases; Gene Expression Regulation; HEK293 Cells; Humans; NF-kappa B; Transfection; Tumor Necrosis Factor-alpha; alpha-Linolenic Acid
PubMed: 27960561
DOI: 10.1080/09637486.2016.1265918 -
Bioprocess and Biosystems Engineering Mar 2021In this study, α-linolenic acid-enriched diacylglycerols (ALA-DAGs) were prepared via a two-step enzymatic way by combi-lipase using silkworm pupae oils as substrates....
In this study, α-linolenic acid-enriched diacylglycerols (ALA-DAGs) were prepared via a two-step enzymatic way by combi-lipase using silkworm pupae oils as substrates. Firstly, several factors including temperature, mass ratio of water to oil, pH and enzyme loading were optimized for the hydrolysis of silkworm pupae oil. The maximum fatty acid content (96.51%) was obtained under the conditions: temperature 40 °C, water/oil 3:2 (w/w), pH 7, lipase TL100L loading 400 U/g, lipase PCL loading 30 U/g. Then, ALA was enriched by urea inclusion, with an increased ALA content of 82.50% being obtained. Secondly, the ALA-enriched silkworm pupae DAG oil (SPDO) was prepared by lipase PCL-catalyzed esterification reaction. After molecular distillation, the final SPDO product contained contents of DAGs (97.01%) and ALA (82.50%). This two-step enzymatic way for production of ALA-DAGs was successfully applied in a 100-fold scale-up reaction. Overall, our study provides a promising way for the preparation of ALA-DAGs.
Topics: Animals; Bombyx; Diglycerides; Lipase; Oils; Pupa; alpha-Linolenic Acid
PubMed: 33159545
DOI: 10.1007/s00449-020-02471-w -
World Review of Nutrition and Dietetics 1994
Review
Topics: Fatty Acids; Fatty Acids, Essential; Humans; Infant; Infant Food; Linoleic Acid; Linoleic Acids; alpha-Linolenic Acid
PubMed: 7871839
DOI: 10.1159/000423557 -
Genes Feb 2022The ω-3 fatty acid desaturase () gene encodes a rate-limiting enzyme in the synthesis of α-linolenic acid. In this study, homologous cloning was used to obtain the...
The ω-3 fatty acid desaturase () gene encodes a rate-limiting enzyme in the synthesis of α-linolenic acid. In this study, homologous cloning was used to obtain the full-length sequence of the gene of . The full-length DNA sequence was 1871 bp long, with 8 exons and 7 introns. The structural analysis of the amino acid sequence revealed that the PvFAD3 protein contained three histidine-conserved regions and an endoplasmic reticulum retention signal. The real-time reverse transcription-polymerase chain reaction performed for determining the expression patterns of the gene in different tissues of showed that expression was highly expressed in the fast oil accumulation stage of seed. The analysis of subcellular localization assay in epidermal cells of tobacco () leaves showed that the PvFAD3 protein was mainly localized in the endoplasmic reticulum. Seed-specific overexpression vectors were constructed, and -mediated genetic transformation was performed to obtain transgenic tobacco plants overexpressing . The results of fatty acid assays performed using harvested seeds showed a significant increase in α-linolenic acid content, a dramatic decrease in linoleic acid content, and an obvious increase in oil content in transgenic tobacco seeds. Collectively, the gene of was confirmed as a key enzyme gene for α-linolenic acid synthesis; thus, indicating that the gene can be used for fatty acid fraction improvement in oilseed plants.
Topics: Euphorbiaceae; Fatty Acids; Plants, Genetically Modified; Seeds; Nicotiana; alpha-Linolenic Acid
PubMed: 35328004
DOI: 10.3390/genes13030450 -
Zhonghua Yi Xue Za Zhi Jan 2013To explore the effects of α-linolenic acid on insulin sensitivity in obese patients.
OBJECTIVE
To explore the effects of α-linolenic acid on insulin sensitivity in obese patients.
METHODS
From October 2011 to April 2012, 16 patients received an oral dose of α-linolenic acid for 8 weeks.Oral glucose tolerance test (OGTT) and insulin releasing test were performed before and after treatment. Homeostasis model assessment insulin resistance (HOMA-IR) index and area under curve of insulin (AUCI) were calculated to evaluate the insulin sensitivity. The levels of serum triglyceride, free fatty acids (FFA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured after an overnight fast.
RESULTS
Obese patients had significantly elevated serum insulin, triglyceride, FFA, IL-6 and TNF-α versus the subjects in normal control group (all P < 0.05). Obese patients were also more insulin-resistant than normal subjects based on a higher HOMA-IR (P < 0.05). Decreased serum insulin, triglyceride, FFA, IL-6 and TNF-α were observed after treatment. With the administration of α-linolenic acid, HOMA-IR and AUCI significantly decreased in obese patients (HOMA-IR: 1.8 ± 0.2 vs 1.2 ± 0.3, P < 0.05; AUCI: 1151 ± 505 vs 768 ± 347, P < 0.05).
CONCLUSION
α-linolenic acid increases peripheral insulin sensitivity in obese patients and it may aid the prevention and treatment of type 2 diabetes mellitus and atherosclerotic vascular diseases.
Topics: Adult; Case-Control Studies; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Prospective Studies; alpha-Linolenic Acid
PubMed: 23648351
DOI: No ID Found -
Metabolism: Clinical and Experimental Apr 2009Higher levels of long-chain n-3 polyunsaturated fatty acids in red blood cell membranes are associated with lower risk of sudden cardiac arrest. Whether membrane levels...
Higher levels of long-chain n-3 polyunsaturated fatty acids in red blood cell membranes are associated with lower risk of sudden cardiac arrest. Whether membrane levels of alpha-linolenic acid, a medium-chain n-3 polyunsaturated fatty acid, show a similar association is unclear. We investigated the association of red blood cell membrane alpha-linolenic acid with sudden cardiac arrest risk in a population-based case-control study. Cases, aged 25 to 74 years, were out-of-hospital sudden cardiac arrest patients attended by paramedics in Seattle, WA (n = 265). Controls, matched to cases by age, sex, and calendar year, were randomly identified from the community (n = 415). All participants were free of prior clinically diagnosed heart disease. Blood was obtained at the time of cardiac arrest (cases) or at the time of an interview (controls). Higher membrane alpha-linolenic acid was associated with a higher risk of sudden cardiac arrest: after adjustment for matching factors and smoking, diabetes, hypertension, education, physical activity, weight, height, and total fat intake, the odds ratios corresponding to increasing quartiles of alpha-linolenic acid were 1.7 (95% confidence interval [CI], 1.0-3.0), 1.9 (95% CI, 1.1-3.3), and 2.5 (95% CI, 1.3-4.8) compared with the lowest quartile. The association was independent of red blood cell levels of long-chain n-3 fatty acids, trans-fatty acids, and linoleic acid. Higher membrane levels of alpha-linolenic acid are associated with higher risk of sudden cardiac arrest.
Topics: Adult; Aged; Death, Sudden, Cardiac; Erythrocyte Membrane; Female; Humans; Male; Middle Aged; Risk Factors; alpha-Linolenic Acid
PubMed: 19303975
DOI: 10.1016/j.metabol.2008.11.013 -
Brain, Behavior, and Immunity Oct 2016Aging is a principal risk factor for neurodegenerative diseases and especially shares similar pathologic mechanisms to Alzheimer's disease (AD). Amyloid-β (Aβ) plaques...
Aging is a principal risk factor for neurodegenerative diseases and especially shares similar pathologic mechanisms to Alzheimer's disease (AD). Amyloid-β (Aβ) plaques deposition and neurofibrillary tangles (NFTs) are the prominent age-dependent pathologies implicated in the cognitive deficits. Accumulation of mis-folded proteins in the endoplasmic reticulum triggers a cellular stress response called the unfolded protein response (UPR), the activation of which is increased in AD patients. However, the UPR relates to the pathological hallmarks of aging is still elusive. In this study, we report that long-term supplement of α-linolenic acid (ALA), starting before the onset of disease symptoms (6month-old), prevents the age-related memory deficits during natural aging. The amelioration of the memory impairment is associated with a decrease in UPR related markers [glucose regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), eukaryotic Initiation Factor 2α (eIF2α)]. ALA suppressed the PERK/eIF2α signaling, which may be responsible for multifaceted memory-deteriorating and neurodegenerative mechanisms, including inhibition of Aβ production by suppressing β-site APP-cleaving enzyme 1 (BACE1) expression, enhancement of cAMP response element binding protein (CREB) function via down-regulating activating transcription factor 4 (ATF4), and suppression of Tau phosphorylation by inhibiting glycogen synthase kinase 3β (GSK-3β) pathway. Taken together, our findings provide new insights into the link between ALA and PERK/eIF2α signaling, which could contribute to a better understanding of an ALA-mediated protective effect in aging-associated neuropathology.
Topics: Aging; Animals; Disease Models, Animal; Female; Memory Disorders; Rats; Rats, Sprague-Dawley; Signal Transduction; alpha-Linolenic Acid; eIF-2 Kinase
PubMed: 26399745
DOI: 10.1016/j.bbi.2015.09.012 -
Bioorganic & Medicinal Chemistry Apr 2018Oxidation products of the poly-unsaturated fatty acids (PUFAs) arachidonic acid, α-linolenic acid and docosahexaenoic acid are bioactive in plants and animals as shown...
Oxidation products of the poly-unsaturated fatty acids (PUFAs) arachidonic acid, α-linolenic acid and docosahexaenoic acid are bioactive in plants and animals as shown for the cyclopentenones prostaglandin 15d-PGJ and PGA, cis-(+)-12-oxophytodienoic acid (12-OPDA), and 14-A-4 neuroprostane. In this study an inexpensive and simple enzymatic multi-step one-pot synthesis is presented for 12-OPDA, which is derived from α-linolenic acid, and the analogous docosahexaenoic acid (DHA)-derived cyclopentenone [(4Z,7Z,10Z)-12-[[-(1S,5S)-4-oxo-5-(2Z)-pent-2-en-1yl]-cyclopent-2-en-1yl] dodeca-4,7,10-trienoic acid, OCPD]. The three enzymes utilized in this multi-step cascade were crude soybean lipoxygenase or a recombinant lipoxygenase, allene oxide synthase and allene oxide cyclase from Arabidopsis thaliana. The DHA-derived 12-OPDA analog OCPD is predicted to have medicinal potential and signaling properties in planta. With OCPD in hand, it is shown that this compound interacts with chloroplast cyclophilin 20-3 and can be metabolized by 12-oxophytodienoic acid reductase (OPR3) which is an enzyme relevant for substrate bioactivity modulation in planta.
Topics: Cyclopentanes; Docosahexaenoic Acids; Molecular Structure; Stereoisomerism; alpha-Linolenic Acid
PubMed: 28818464
DOI: 10.1016/j.bmc.2017.07.061