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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 -
Mediators of Inflammation 2020The neurotrophin brain-derived neurotrophic factor (BDNF) affects poststroke functional outcome, neurogenesis, neuroprotection, and neuroplasticity. Its level is related...
OBJECTIVE
The neurotrophin brain-derived neurotrophic factor (BDNF) affects poststroke functional outcome, neurogenesis, neuroprotection, and neuroplasticity. Its level is related to the diet and nutritional status, and more specifically, it is free fatty acids (FFAs) and eicosanoids that can have an impact on the BDNF level. The aim of this study was to analyze the potential impact of FFAs and eicosanoids on the BDNF level in stroke patients. . Seventy-three ischemic stroke patients were prospectively enrolled in the study. Laboratory tests were performed in all subjects, including the levels of FFAs, eicosanoids, and BDNF. FFAs and inflammatory metabolites were determined by gas chromatography and liquid chromatography, while BDNF was evaluated by the immune-enzymatic method (ELISA).
RESULTS
The plasma level of BDNF negatively correlated with C22:1n9 13 erucic acid, C18:3n3 linolenic acid (ALA), and lipoxin A4 15-epi-LxA4. A direct association was observed in relation to BDNF and C16:1 palmitoleic acid and C20:3n6 eicosatrienoic acid (dihomo-gamma-linolenic acid (DGLA)).
CONCLUSIONS
Saturated fatty acids and omega-3 and omega-9 erucic acids can affect signaling in the BDNF synthesis resulting in the decrease in BDNF. There is a beneficial effect of DGLA on the BDNF level, while the effect of ALA on BDNF can be inhibitory. Specialized proresolving lipid mediators can play a role in the BDNF metabolism. BDNF can interact with inflammation as the risk factor in the cardiovascular disorders, including stroke.
Topics: 8,11,14-Eicosatrienoic Acid; Adult; Aged; Aged, 80 and over; Brain-Derived Neurotrophic Factor; Eicosanoids; Fatty Acids, Nonesterified; Female; Humans; Male; Middle Aged; Prospective Studies; Stroke
PubMed: 33343231
DOI: 10.1155/2020/6676247 -
Journal, Genetic Engineering &... Mar 2022Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They are synthesized endogenously in humans, though... (Review)
Review
BACKGROUND
Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They are synthesized endogenously in humans, though not fully compensating all body requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including anti-inflammatory and anti-cancer characters. This review capitalizes on the major omega-9 pharmacological activities in context of inflammation management for its different natural forms in different dietary sources. The observed anti-inflammatory effects reported for oleic acid (OA), mead acid, and erucic acid were directed to attenuate inflammation in several physiological and pathological conditions such as wound healing and eye inflammation by altering the production of inflammatory mediators, modulating neutrophils infiltration, and altering VEGF effector pathway. OA action mechanisms as anti-tumor agent in different cancer types are compiled for the first time based on its anti- and pro-carcinogenic actions.
CONCLUSION
We conclude that several pathways are likely to explain the anti-proliferative activity of OA including suppression of migration and proliferation of breast cancer cells, as well stimulation of tumor suppressor genes. Such action mechanisms warrant for further supportive clinical and epidemiological studies to confirm the beneficial outcomes of omega-9 consumption especially over long-term intervention.
PubMed: 35294666
DOI: 10.1186/s43141-022-00329-0 -
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 -
Expert Review of Neurotherapeutics Sep 2008X-linked adrenoleukodystrophy (X-ALD; OMIM #300100) is caused by defects of the ABCD1 gene on chromosome Xq28, resulting in an impairment of peroxisomal beta-oxidation... (Review)
Review
X-linked adrenoleukodystrophy (X-ALD; OMIM #300100) is caused by defects of the ABCD1 gene on chromosome Xq28, resulting in an impairment of peroxisomal beta-oxidation and the accumulation of saturated very long chain fatty acids (VLCFAs). Primary manifestations occur in the CNS, the adrenal cortex and the testes' Leydig cells. The clinical presentation shows a marked variability which is not explained by the different X-ALD genotypes. Phenotypes range from rapidly progressive cerebral disease with childhood (childhood cerebral ALD [CCALD]) or adulthood (adult cerebral ALD [ACALD]) onset leading to death within a few years, over adult-onset adrenomyeloneuropathy (AMN) with or without focal CNS demyelination, AMN converting into a rapidly progressive, cerebral demyelinating phenotype resembling CCALD, to slow disease progression over decades, or adrenal insufficiency only. Approximately 50% of female heterozygotes develop moderate spastic paresis resembling the AMN phenotype. This review focuses on current experiences with different therapeutic approaches. Lorenzo's oil did not prove to be effective in cerebral inflammatory disease variants, but asymptomatic patients, and speculatively AMN variants without cerebral involvement, as well as female carriers may benefit from early intake of oleic and erucic acids in addition to VLCFA restriction. Hormone-replacement therapy is necessary in all patients with adrenal insufficiency. Hematopoietic stem cell transplantation has been reported to be effective in presymptomatic or early symptomatic CCALD, and may well also be a final therapeutic option in early ACALD patients. Early detection of mutation carriers and timely initiation of therapy is important for the effectiveness of all therapeutic efforts. Gene therapy of endogenous hematopoietic stem cells, pharmacological upregulation of other genes encoding proteins involved in peroxisomal beta-oxidation, reduction of oxidative stress, and possibly lovastatin are candidates for future X-ALD therapies.
Topics: Adrenoleukodystrophy; Animals; Clinical Trials as Topic; Drug Combinations; Erucic Acids; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Triolein
PubMed: 18759549
DOI: 10.1586/14737175.8.9.1367 -
Animals : An Open Access Journal From... Sep 2019Soybean meal (SBM) is a byproduct from the oil-industry widely used as protein supplement to ruminants worldwide due to its nutritional composition, high protein... (Review)
Review
Soybean meal (SBM) is a byproduct from the oil-industry widely used as protein supplement to ruminants worldwide due to its nutritional composition, high protein concentration, and availability. However, the dependency on monocultures such as SBM is problematic due to price fluctuation, availability and, in some countries, import dependency. In this context, oilseeds from the mustard family such as rapeseed/canola ( and ), camelina (), and carinata () have arisen as possible alternative protein supplements for ruminants. Therefore, the objective of this comprehensive review was to summarize results from studies in which canola meal (CM), camelina meal (CMM), and carinata meal (CRM) were fed to ruminants. This review was based on published peer-reviewed articles that were obtained based on key words that included the oilseed plant in question and words such as "ruminal fermentation and metabolism, animal performance, growth, and digestion". Byproducts from oil and biofuel industries such as CM, CMM, and CRM have been evaluated as alternative protein supplements to ruminants in the past two decades. Among the three plants reviewed herein, CM has been the most studied and results have shown an overall improvement in nitrogen utilization when animals were fed CM. Camelina meal has a comparable amino acids (AA) profile and crude protein (CP) concentration to CM. It has been reported that by replacing other protein supplements with CMM in ruminant diets, similar milk and protein yields, and average daily gain have been observed. Carinata meal has protein digestibility similar to SBM and its CP is highly degraded in the rumen. Overall, we can conclude that CM is at least as good as SBM as a protein supplement; and although studies evaluating the use of CMN and CRM for ruminants are scarce, it has been demonstrated that both oilseeds may be valuable feedstuff for livestock animals. Despite the presence of erucic acid and glucosinolates in rapeseed, no negative effect on animal performance was observed when feeding CM up to 20% and feeding CMN and CRM up to 10% of the total diet.
PubMed: 31546983
DOI: 10.3390/ani9100704 -
Open Medicine (Warsaw, Poland) 2017We evaluated the free fatty acids differences in plasma between hyperemesis gravidarum(HG) and healthy pregnant in first trimester pregnancy.
UNLABELLED
We evaluated the free fatty acids differences in plasma between hyperemesis gravidarum(HG) and healthy pregnant in first trimester pregnancy.
OBJECTIVE
We aimed to compare the plasma levels of DHA, AA and EPA, between HG patients and healthy pregnant women.
DESIGN
Fifty-two pregnants were involved in the study. Twenty-six pregnants of them were HG as study group, and twenty-six pregnants were enrolled as healthy pregnant women at the similar gestational age. The saturated fatty acids C14, C15, C16, C18, C20, C22, and C24; the omega-3 fatty acids eicosapentaenoic acid, (EPA) and docosahexaenoic acid, (DHA); the omega-6 fatty acids linoleic acid, arachidonic acid (AA), and homo-gamma-linolenic acid; and the omega-9 fatty acids oleic acid, erucic acid, and nervonic acid were analysed by gas chromatography.
RESULTS
Statistically differences was not seen between the groups with maternal age, gestational age, or plasma levels of EPA, DHA, and AA. Statistically significant difference was seen between the groups with plasma levels of C20 and C22(p0.05). C20 was declined but C22 was rised in the HG patients.
CONCLUSION
EPA, DHA, or AA, which related to placental and fetal neural development are not changing from Hyperemesis gravidarum.
PubMed: 28730165
DOI: 10.1515/med-2017-0009 -
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 -
Nutrients Mar 2023The increase in life expectancy led to a significant rise in the prevalence of age-related neurological diseases, such as cognitive impairment, dementia, and Alzheimer's...
UNLABELLED
The increase in life expectancy led to a significant rise in the prevalence of age-related neurological diseases, such as cognitive impairment, dementia, and Alzheimer's disease. Although genetics certainly play a role, nutrition emerged as a key factor in maintaining optimal cognitive function among older adults. Therefore, the study aimed to investigate whether specific categories and subcategories of dietary fats, based on carbon-chain length, are associated with cognitive status in a cohort of 883 Italian participants over the age of 50.
METHODS
The intake of total, single class of dietary fat, such as saturated fatty acids (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA), and also single fatty acids grouped according to carbon-chain length, were evaluated by food frequency questionnaires (FFQs). Cognitive health was assessed using the short portable mental status questionnaire (SPMSQ).
RESULTS
After adjustment for potential confounding factors subjects with a moderate consumption of both short-chain SFA (for Q2 vs. Q1, OR = 0.23, 95% CI: 0.08, 0.66) and middle-chain SFA specifically lauric acid (C12:0) intake (for Q2 vs. Q1, OR = 0.27, 95% CI: 0.09, 0.77) were less likely to suffer from cognitive impairment. Among single MUFAs, erucic acid (C22:1) intake resulted in an inverse association, in a linear way, with cognitive impairment (for Q4 vs. Q1, OR = 0.04, 95% CI: 0.00, 0.39). Conversely, moderate intake of linoleic acid (C18:2) was associated with cognitive impairment (Q3 vs. Q1, OR = 4.59, 95% CI: 1.51, 13.94). Regarding other PUFAs, individuals consuming moderate intake alpha linolenic acid (C18:3) were less likely to have cognitive impairment (for Q3 vs. Q1, OR = 0.19, 95% CI: 0.06, 0.64).
CONCLUSIONS
Total SFA intake appeared to be inversely associated with cognitive impairment. Regarding specific subtypes of fatty acids, the results mostly referred to short- and middle-chain SFA. Further studies are needed to validate the results of the present study.
Topics: Humans; Aged; Dietary Fats; Fatty Acids; Fatty Acids, Unsaturated; Fatty Acids, Monounsaturated; Cognition
PubMed: 36986159
DOI: 10.3390/nu15061429 -
Clinical Cardiology Sep 1994Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the... (Review)
Review
Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the toxic oil syndrome, include pulmonary hypertension and right ventricular hypertrophy plus widespread vascular and neural lesions in other organs. Many of the late deaths ended with a scleroderma-like illness. Because scleroderma involves the heart, an examination was made of the small and large coronary arteries, the neural structures, and the conduction system from 11 victims dying with the toxic oil syndrome. Dense fibrosis, atrionodal junctional hemorrhages, and cystic degeneration of the sinus nodes were present. Small and large coronary arteries exhibited focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration. This latter abnormality was associated with sloughing of the inner wall and embolization of the detached fragment downstream in the same coronary artery. Every heart had many degenerative lesions within nerves, ganglia, and the coronary chemoreceptor. Based upon observations by others with experimental feeding of rapeseed oil containing either high or low erucic acid, it is suggested that this oil must remain a major suspected cause of the toxic oil syndrome, particularly in conjunction with some as yet unexplained facilitative influence by oleoanilids. If this is so, it is important to reexamine the widely recommended use of any rapeseed oil product as a suitable food for humans or animals.
Topics: Brassica; Fatty Acids, Monounsaturated; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Plant Oils; Rapeseed Oil; Scleroderma, Systemic; Spain; Syndrome
PubMed: 8001309
DOI: 10.1002/clc.4960170902