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Cell Metabolism May 2023Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches to...
Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches to comprehensively assess the diverse FFAs circulating in human plasma. Furthermore, assessing how FFA-mediated processes interact with genetic risk for disease remains elusive. Here, we report the design and implementation of fatty acid library for comprehensive ontologies (FALCON), an unbiased, scalable, and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids associated with decreased membrane fluidity. Furthermore, we prioritized genes that reflect the combined effects of harmful FFA exposure and genetic risk for type 2 diabetes (T2D). We found that c-MAF-inducing protein (CMIP) protects cells from FFA exposure by modulating Akt signaling. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism.
Topics: Humans; Fatty Acids, Nonesterified; Diabetes Mellitus, Type 2; Fatty Acids; Signal Transduction; Biology
PubMed: 37075753
DOI: 10.1016/j.cmet.2023.03.018 -
Roczniki Panstwowego Zakladu Higieny 2018The garden nasturtium (Tropaeolum majus L.) belongs to the family Tropaeolaceae. Native to South America it was brought to Europe in XVI century. It is a plant with... (Review)
Review
The garden nasturtium (Tropaeolum majus L.) belongs to the family Tropaeolaceae. Native to South America it was brought to Europe in XVI century. It is a plant with numerous healing properties. Medicinal plants such as the garden nasturtium contain trace elements and bioactive compounds which can be easily absorbed by the human body. The flowers and other parts of the garden nasturtium are a good source of micro elements such as potassium, phosphorus, calcium and magnesium, and macro elements, especially of zinc, copper and iron. The essential oil, the extract from the flowers and leaves, and the compounds isolated from these elements have antimicrobial, antifungal, hypotensive, expectorant and anticancer effects. Antioxidant activity of extracts from garden nasturtium is an effect of its high content of compounds such as anthocyanins, polyphenols and vitamin C. Due to its rich phytochemical content and unique elemental composition, the garden nasturtium may be used in the treatment of many diseases for example the illnesses of the respiratory and digestive systems. High content of erucic acid in nasturtium seeds makes it possible to use its oil as treatment in adrenoleukodystrophy. It is also applied in dermatology because it improves the condition of skin and hair. More recently, the flowers of this species have been used as a decorative and edible element of some types of dishes. Aim of the review was to summarize available data concerning garden nasturtium Tropaeolum majus L.
Topics: Antioxidants; Flowers; Humans; Plant Extracts; Trace Elements; Tropaeolum
PubMed: 29766690
DOI: No ID Found -
The Journal of Biological Chemistry Apr 2023Imbalances in the amounts of amyloid-β peptides (Aβ) generated by the membrane proteases β- and γ-secretase are considered as a trigger of Alzheimer's disease (AD)....
Imbalances in the amounts of amyloid-β peptides (Aβ) generated by the membrane proteases β- and γ-secretase are considered as a trigger of Alzheimer's disease (AD). Cell-free studies of γ-secretase have shown that increasing membrane thickness modulates Aβ generation but it has remained unclear if these effects are translatable to cells. Here we show that the very long-chain fatty acid erucic acid (EA) triggers acyl chain remodeling in AD cell models, resulting in substantial lipidome alterations which included increased esterification of EA in membrane lipids. Membrane remodeling enhanced γ-secretase processivity, resulting in the increased production of the potentially beneficial Aβ37 and/or Aβ38 species in multiple cell lines. Unexpectedly, we found that the membrane remodeling stimulated total Aβ secretion by cells expressing WT γ-secretase but lowered it for cells expressing an aggressive familial AD mutant γ-secretase. We conclude that EA-mediated modulation of membrane composition is accompanied by complex lipid homeostatic changes that can impact amyloidogenic processing in different ways and elicit distinct γ-secretase responses, providing critical implications for lipid-based AD treatment strategies.
Topics: Humans; Amyloid Precursor Protein Secretases; Membrane Lipids; Amyloid beta-Peptides; Alzheimer Disease; Cell Line; Amyloid beta-Protein Precursor; Presenilin-1
PubMed: 36805335
DOI: 10.1016/j.jbc.2023.103027 -
Frontiers in Plant Science 2022Erucic acid (C22:1, ω-9, EA) is a very-long-chain monounsaturated fatty acid (FA) that is an important oleochemical product with a wide range of uses in metallurgy,... (Review)
Review
Erucic acid (C22:1, ω-9, EA) is a very-long-chain monounsaturated fatty acid (FA) that is an important oleochemical product with a wide range of uses in metallurgy, machinery, rubber, the chemical industry, and other fields because of its hydrophobicity and water resistance. EA is not easily digested and absorbed in the human body, and high-EA rapeseed (HEAR) oil often contains glucosinolates. Both glucosinolates and EA are detrimental to health and can lead to disease, which has resulted in strict guidelines by regulatory bodies on maximum EA contents in oils. Increasingly, researchers have attempted to enhance the EA content in Brassicaceae oilseeds to serve industrial applications while conversely reducing the EA content to ensure food safety. For the production of both LEAR and HEAR, biotechnology is likely to play a fundamental role. Elucidating the metabolic pathways of EA can help inform the improvement of Brassicaceae oilseeds through transgenic technology. In this paper, we introduce the industrial applications of HEAR oil and health benefits of low-EA rapeseed (LEAR) oil first, following which we review the biosynthetic pathways of EA, introduce the EA resources from plants, and focus on research related to the genetic engineering of EA in Brassicaceae oilseeds. In addition, the effects of the environment on EA production are addressed, and the safe cultivation of HEAR and LEAR is discussed. This paper supports further research into improving FAs in Brassicaceae oilseeds through transgenic technologies and molecular breeding techniques, thereby advancing the commercialization of transgenic products for better application in various fields.
PubMed: 35645989
DOI: 10.3389/fpls.2022.899076 -
Molecules (Basel, Switzerland) Feb 2023Erucic acid (EA) is monounsaturated fatty acid (22:1 n-9), synthesized in the seeds of many plants from the family, with , , or considered as its richest source. As... (Review)
Review
Erucic acid (EA) is monounsaturated fatty acid (22:1 n-9), synthesized in the seeds of many plants from the family, with , , or considered as its richest source. As the compound has been blamed for the poisoning effect in Toxic Oil Syndrome, and some data indicated its cardiotoxicity to rats, EA has been for decades classified as toxic substance, the use of which should be avoided. However, the cardiac adverse effects of EA have not been confirmed in humans, and the experiments in animal models had many limitations. Thus, the aim of this review was to present the results of the so far published studies on both toxic, and pharmacological properties of EA, trying to answer the question on its future medicinal use. Despite the ambiguous and relatively small data on toxic and beneficial effects of EA it seems that the compound is worth investigating. Further research should be particularly directed at the verification EA toxicity, more in-depth studies on its neuroprotective and cytotoxic properties, but also its use in combination with other drugs, as well as its role as a drug carrier.
Topics: Humans; Rats; Animals; Erucic Acids; Fatty Acids, Monounsaturated; Brassica napus; Seeds
PubMed: 36838911
DOI: 10.3390/molecules28041924 -
Microbial Cell Factories Jul 2022Very long chain fatty acids (VLCFA) and their derivatives are industrially attractive compounds. The most important are behenic acid (C22:0) and erucic acid (C22:1Δ),...
BACKGROUND
Very long chain fatty acids (VLCFA) and their derivatives are industrially attractive compounds. The most important are behenic acid (C22:0) and erucic acid (C22:1Δ), which are used as lubricants, and moisturizers. C22:0 and C22:1Δ have also potential for biofuel production. These fatty acids are conventionally obtained from plant oils. Yarrowia lipolytica is an oleaginous yeast with a long history of gene manipulations resulting in the production of industrially interesting compounds, such as organic acids, proteins, and various lipophilic molecules. It has been shown previously that it has potential for the production of VLCFA enriched single cell oils.
RESULTS
The metabolism of Y. lipolytica was redesigned to achieve increased production of VLCFA. The effect of native diacylglycerol acyltransferases of this yeast YlLro1p, YlDga1p, and YlDga2p on the accumulation of VLCFA was examined. It was found that YlDga1p is the only enzyme with a beneficial effect. Further improvement of accumulation was achieved by overexpression of 3-ketoacyl-CoA synthase (TaFAE1) under 8UAS-pTEF promoter and blockage fatty acid degradation pathway by deletion of YlMFE1. The best-producing strain YL53 (Δmfe, pTEF-YlDGA1, 8UAS-pTEF-TaFAE1) produced 120 µg of very long chain fatty acids per g of produced biomass, which accounted for 34% of total fatty acids in biomass.
CONCLUSIONS
Recombinant strains of Y. lipolytica have proved to be good producers of VLCFA. Redesign of lipid metabolism pathways had a positive effect on the accumulation of C22:1Δ and C22:0, which are technologically attractive compounds.
Topics: Biofuels; Biomass; Diacylglycerol O-Acyltransferase; Fatty Acids; Yarrowia
PubMed: 35818073
DOI: 10.1186/s12934-022-01866-6 -
Nutrients Oct 2018The European Food Safety Authority (EFSA) published a risk assessment of erucic acid (22:1n-9) in 2016, establishing a Tolerable Daily Intake (TDI) for humans of 7 mg kg...
The European Food Safety Authority (EFSA) published a risk assessment of erucic acid (22:1n-9) in 2016, establishing a Tolerable Daily Intake (TDI) for humans of 7 mg kg body weight per day. This report largely excluded the contribution of erucic acid from fish and seafood, due to this fatty acid often not being reported separately in seafood. The Institute of Marine Research (IMR) in Norway analyzes erucic acid and has accumulated extensive data from analyses of fish feeds, farmed and wild fish, and seafood products. Our data show that rapeseed oil (low erucic acid varieties) and fish oil are the main sources of erucic acid in feed for farmed fish. Erucic acid content increases with total fat content, both in farmed and wild fish, and it is particularly high in fish liver, fish oil, and oily fish, such as mackerel. We show that the current TDI could be exceeded with a 200 g meal of mackerel, as at the maximum concentration analyzed, such a meal would contribute 143% to the TDI of a 60 kg person. These data cover a current knowledge gap in the scientific literature regarding the content of erucic acid in fish and seafood.
Topics: Adipose Tissue; Animal Feed; Animals; Animals, Wild; Diet; Dietary Fats; Environmental Exposure; Erucic Acids; Europe; Fish Oils; Fisheries; Fishes; Food Contamination; Food Safety; Humans; Norway; Perciformes; Rapeseed Oil; Seafood
PubMed: 30301170
DOI: 10.3390/nu10101443 -
Foods (Basel, Switzerland) Sep 2021Mustard plants have been widely cultivated and used as spice, medicine and as source of edible oils. Currently, the use of the seeds of the mustard species (white... (Review)
Review
Mustard plants have been widely cultivated and used as spice, medicine and as source of edible oils. Currently, the use of the seeds of the mustard species (white mustard or yellow mustard), (brown mustard) and (black mustard) in the food and beverage industry is immensely growing due to their nutritional and functional properties. The seeds serve as a source for a wide range of biologically active components including isothiocyanates that are responsible for the specific flavor of mustard, and tend to reveal conflicting results regarding possible health effects. Other potentially undesirable or toxic compounds, such as bisphenol F, erucic acid or allergens, may also occur in the seeds and in mustard products intended for human consumption. The aim of this article is to provide comprehensive information about potentially harmful compounds in mustard seeds and to evaluate potential health risks as an increasing use of mustard seeds is expected in the upcoming years.
PubMed: 34574199
DOI: 10.3390/foods10092089 -
Plant Biotechnology Journal Feb 2014Erucic acid is a valuable industrial fatty acid with many applications. The main producers of this acid are today high erucic rapeseed (Brassica napus) and mustard...
Erucic acid is a valuable industrial fatty acid with many applications. The main producers of this acid are today high erucic rapeseed (Brassica napus) and mustard (Brassica juncea), which have 45%-50% of erucic acid in their seed oils. Crambe abyssinica is an alternative promising producer of this acid as it has 55%-60% of erucic acid in its oil. Through genetic modification (GM) of three genes, we have previously increased the level of erucic acid to 71% (68 mol%) in Crambe seed oil. In this study, we further investigated different aspects of oil biosynthesis in the developing GM Crambe seeds in comparison with wild-type (Wt) Crambe, rapeseed and safflower (Carthamus tinctorius). We show that Crambe seeds have very low phosphatidylcholine-diacylglycerol interconversion, suggesting it to be the main reason why erucic acid is limited in the membrane lipids during oil biosynthesis. We further show that GM Crambe seeds have slower seed development than Wt, accompanied by slower oil accumulation during the first 20 days after flowering (DAF). Despite low accumulation of erucic acid during early stages of GM seed development, nearly 86 mol% of all fatty acids accumulated between 27 and 50 DAF was erucic acid, when 40% of the total oil is laid down. Likely bottlenecks in the accumulation of erucic acid during early stages of GM Crambe seed development are discussed.
Topics: Acylation; Brassica; Brassica rapa; Carbon Radioisotopes; Chlorophyll; Crambe Plant; Erucic Acids; Fatty Acids; Genetic Engineering; Glycerol; Plant Oils; Plants, Genetically Modified; Seeds; Time Factors
PubMed: 24119222
DOI: 10.1111/pbi.12128 -
Foods (Basel, Switzerland) Mar 2022Rapeseed meal and pressed cake are protein-rich by-products from rapeseed after oil extraction. Because of the high protein content, these by-products are an important...
Rapeseed meal and pressed cake are protein-rich by-products from rapeseed after oil extraction. Because of the high protein content, these by-products are an important source of food protein. Their use is motivated by the current pressure on protein prices, increasing demand for functional ingredients, and remaining controversy over wider use of soy. During process development for protein extraction from rapeseed cake or meal, special attention needs to be given to compounds such as erucic acid, which can cause problems if consumed in high amounts. Erucic acid determination is critical to ensure safety, since protein extraction procedures could lead to concentration of this compound in the final product. This research compared differences in extraction (Soxhlet and Folch) and derivatization techniques to obtain the highest erucic acid yield from rapeseed protein products. Results showed that no erucic acid accumulation occurred in the protein during its extraction from the rapeseed cake. The Soxhlet procedure was superior to Folch, as it yielded the highest concentrations of erucic acid. Furthermore, with the Folch procedure, some natural cis-configuration of erucic acid converted to its corresponding trans-configuration (brassidic acid). The latter is important, as ignoring this phenomenon can lead to underestimation of erucic acid content in rapeseed protein samples.
PubMed: 35327237
DOI: 10.3390/foods11060815