-
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 2019() is the world's most widely grown temperate oilseed crop. Although breeding for human consumption has led to removal of erucic acid from refined canola oils, there is...
() is the world's most widely grown temperate oilseed crop. Although breeding for human consumption has led to removal of erucic acid from refined canola oils, there is renewed interest in the industrial uses of erucic acid derived from , and there is a rich germplasm available for use. Here, low- and high-erucic acid accessions of seeds were examined for the distribution of erucic acid-containing lipids and the gene transcripts encoding the enzymes involved in pathways for its incorporation into triacylglycerols (TAGs) across the major tissues of the seeds. In general, the results indicate that a heterogeneous distribution of erucic acid across seed tissues was contributed by two isoforms (out of six) of ( and a combination of phospholipid:diacylglycerol acyltransferase (PDAT)- and diacylglycerol acyltransferase (DGAT)-mediated incorporation of erucic acid into TAGs in cotyledonary tissues. An absence of the expression of these two isoforms accounted for the absence of erucic acid in the TAGs of the low-erucic accession.
PubMed: 32082336
DOI: 10.3389/fpls.2019.01744 -
Nutrients Mar 2018Regular foetal development is crucial for assuring good health status in the offspring. The quality and quantity of maternal dietary fatty acids (FAs) can affect growth.... (Comparative Study)
Comparative Study
Regular foetal development is crucial for assuring good health status in the offspring. The quality and quantity of maternal dietary fatty acids (FAs) can affect growth. The study aimed to: (1) investigate the association of maternal/foetal lipid profiles with birth weight (BW); and (2) compare these profiles in small, appropriate, and large for gestational age (SGA, AGA, and LGA) infants. FAs were measured in erythrocyte membranes using gas chromatography analysis in 607 mother-infant pairs (316 males, 52.1%). In the quantile regression, a significant association between BW and levels of maternal linoleic acid (LA; C18:2, n-6; coefficient: 18.66; = 0.010), arachidonic acid (AA; C20:4, n-6; coefficient: 11.35; = 0.007), docosahexaenoic acid (DHA; C22:6, n-3; coefficient: 29.73; = 0.007), polyunsaturated FAs (coefficient: 8.55; = 0.001), foetal DHA (coefficient: -22.82; = 0.037), and saturated FAs (coefficient: -65.41; = 0.002) was found. Myristic (C14:0) and pentadecanoic acids (C15:0), both maternal ( = 0.000; = 0.017) and foetal ( = 0.009; = 0.002), and maternal erucic acid (C22:1, n-9; = 0.026) were found at higher levels in SGA infants as compared to AGA ones. Conversely, maternal LA, AA, and omega 6 FAs levels were higher in AGA infants ( = 0.037; = 0.003; = 0.026, respectively). Maternal and foetal polyunsaturated and omega 6 FAs levels are positively related to BW, while a lipid profile rich in saturated FAs and erucic acid may influence the risk of SGA.
Topics: Adult; Birth Weight; Erythrocytes; Fatty Acids; Fatty Acids, Omega-6; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Maternal Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Risk Factors
PubMed: 29570689
DOI: 10.3390/nu10040402 -
Frontiers in Nutrition 2023A previous double-blind, randomized clinical trial of 42 healthy individuals conducted with N6.2 found that the probiotic's mechanistic tryptophan pathway was...
A previous double-blind, randomized clinical trial of 42 healthy individuals conducted with N6.2 found that the probiotic's mechanistic tryptophan pathway was significantly modified when the data was stratified based on the individuals' lactic acid bacteria (LAB) stool content. These results suggest that confounding factors such as dietary intake which impact stool LAB content may affect the response to the probiotic treatment. Using dietary intake, serum metabolite, and stool LAB colony forming unit (CFU) data from a previous clinical trial, the relationships between diet, metabolic response, and fecal LAB were assessed. The diets of subject groups with high vs. low CFUs of LAB/g of wet stool differed in their intakes of monounsaturated fatty acids, vegetables, proteins, and dairy. Individuals with high LAB consumed greater amounts of cheese, fermented meats, soy, nuts and seeds, alcoholic beverages, and oils whereas individuals with low LAB consumed higher amounts of tomatoes, starchy vegetables, and poultry. Several dietary variables correlated with LAB counts; positive correlations were determined for nuts and seeds, fish high in N-3 fatty acids, soy, and processed meats, and negative correlations to consumption of vegetables including tomatoes. Using machine learning, predictors of LAB count included cheese, nuts and seeds, fish high in N-3 fatty acids, and erucic acid. Erucic acid alone accurately predicted LAB categorization, and was shown to be utilized as a sole fatty acid source by several species regardless of their mode of fermentation. Several metabolites were significantly upregulated in each group based on LAB titers, notably polypropylene glycol, caproic acid, pyrazine, and chondroitin sulfate; however, none were correlated with the dietary intake variables. These findings suggest that dietary variables may drive the presence of LAB in the human gastrointestinal tract and potentially impact response to probiotic interventions.
PubMed: 37153913
DOI: 10.3389/fnut.2023.1118679 -
Indian Journal of Pharmacology 2023The objective of this study was to investigate the potential for erucic acid (EA), an omega-9 monounsaturated fatty acid, to act as a neuroprotective agent.
OBJECTIVE
The objective of this study was to investigate the potential for erucic acid (EA), an omega-9 monounsaturated fatty acid, to act as a neuroprotective agent.
MATERIALS AND METHODS
In this study, EA was investigated against N2a cell lines and a rotenone (ROT)-induced model of Parkinson's disease for its neuroprotective potential. The N2a cell line was incubated with fetal bovine serum, penicillin, and streptomycin supplemented with Dulbecco's Modified Eagle's Medium, and the following assays were carried out: (i) MTT, (ii) biocompatibility, (iii) DCFDA, and (iv) diphenylamine. A cell morphology study was also performed. Further, ROT 1 mg/kg s.c. and EA 3 and 10 mg/kg p.o. were given to rats on a daily basis for 21 days, and the following parameters were assessed: (i) neurobehavioral studies, (ii) oxidative stress markers, (iii) neuroinflammatory markers, (iv) neurotransmitters, and (v) histopathological study.
RESULTS
The cell viability assay revealed that EA showed protection against ROT-induced toxicity in N2a cells, which was confirmed by a cell morphology study. EA decreased oxidative stress and % DNA fragmentation significantly. EA also prevented ROT-induced motor impairment and altered levels of oxidative stress markers, neurotransmitters, and neuroinflammatory markers significantly. When compared to the ROT group, a histological investigation of the EA group showed partial neuronal loss with the existence of intact neurons in between the vacuolated gaps.
CONCLUSION
This study revealed that EA possesses profound neuroprotective properties in in vitro and in vivo studies. Additional research can be carried out to study the mechanism of EA with respect to its neuroprotective potential.
Topics: Rats; Animals; Parkinson Disease; Rotenone; Oxidative Stress; Neuroprotective Agents; Neurotransmitter Agents
PubMed: 38174534
DOI: 10.4103/ijp.ijp_314_23 -
Poultry Science Sep 2020In this study, we evaluated the body fat distribution and fatty acid composition of muscles and adipose tissues of Yangzhou geese, including thirty 60-day-old goslings...
In this study, we evaluated the body fat distribution and fatty acid composition of muscles and adipose tissues of Yangzhou geese, including thirty 60-day-old goslings (15 males and 15 females) and 20 320-day-old geese (10 males and 10 females). Adipose tissues of Yangzhou geese were distributed widely and could be divided into 5 types: subcutaneous fat, abdominal fat, sartorial fat, neck fat, and mesenteric fat. Higher contents of abdominal fat, sartorial fat, neck fat, and mesenteric fat but a lower content of subcutaneous fat were found in adult geese than in goslings (P ≤ 0.05). Adult female geese deposited more fat than adult male geese (P ≤ 0.05). No difference was found in the fat distribution and fat content between male and female goslings (P > 0.05). The breast muscle of adult geese was characterized by a higher content of total monounsaturated fatty acids (ΣMUFAs) and a lower content of n-6 polyunsaturated fatty acids (ΣPUFAs n-6) than that of goslings (P ≤ 0.05). Lower concentrations of total saturated fatty acids and ΣPUFA were found in adult female geese than in female goslings (P ≤ 0.05). In comparison with adult female geese, the breast muscle of adult male geese had higher total saturated fatty acids and stearic acid (P ≤ 0.05). For the thigh muscle, adult female geese had a higher ΣMUFAs content than adult male geese (P ≤ 0.05). In adipose tissues, adult geese had a higher Σn-6/Σn-3 ratio but had lower contents of erucic acid, linolenic acid, arachidonic acid, docosatetraenoic acid, and ΣPUFA n-3 than goslings, and adult female geese had a higher ΣMUFAs content than adult male geese (P ≤ 0.05). In conclusion, adult geese, especially adult female geese, accumulated more fat than goslings. Both age and sex affected the fatty acid composition of muscles and adipose tissues in geese. This research provides essential information not only for the nutritional evaluation of geese but also for the consumption and processing of goose products.
Topics: Adipose Tissue; Animals; Body Composition; Body Fat Distribution; Fatty Acids; Female; Geese; Male; Meat; Muscle, Skeletal
PubMed: 32868008
DOI: 10.1016/j.psj.2020.05.052 -
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 -
The Journal of Biological Chemistry Jul 2020Feeding of rapeseed (canola) oil with a high erucic acid concentration is known to cause hepatic steatosis in animals. Mitochondrial fatty acid oxidation plays a central...
Feeding of rapeseed (canola) oil with a high erucic acid concentration is known to cause hepatic steatosis in animals. Mitochondrial fatty acid oxidation plays a central role in liver lipid homeostasis, so it is possible that hepatic metabolism of erucic acid might decrease mitochondrial fatty acid oxidation. However, the precise mechanistic relationship between erucic acid levels and mitochondrial fatty acid oxidation is unclear. Using male Sprague-Dawley rats, along with biochemical and molecular biology approaches, we report here that peroxisomal β-oxidation of erucic acid stimulates malonyl-CoA formation in the liver and thereby suppresses mitochondrial fatty acid oxidation. Excessive hepatic uptake and peroxisomal β-oxidation of erucic acid resulted in appreciable peroxisomal release of free acetate, which was then used in the synthesis of cytosolic acetyl-CoA. Peroxisomal metabolism of erucic acid also remarkably increased the cytosolic NADH/NAD ratio, suppressed sirtuin 1 (SIRT1) activity, and thereby activated acetyl-CoA carboxylase, which stimulated malonyl-CoA biosynthesis from acetyl-CoA. Chronic feeding of a diet including high-erucic-acid rapeseed oil diminished mitochondrial fatty acid oxidation and caused hepatic steatosis and insulin resistance in the rats. Of note, administration of a specific peroxisomal β-oxidation inhibitor attenuated these effects. Our findings establish a cross-talk between peroxisomal and mitochondrial fatty acid oxidation. They suggest that peroxisomal oxidation of long-chain fatty acids suppresses mitochondrial fatty acid oxidation by stimulating malonyl-CoA formation, which might play a role in fatty acid-induced hepatic steatosis and related metabolic disorders.
Topics: Animals; Erucic Acids; Fatty Liver; Insulin Resistance; Liver; Male; Malonyl Coenzyme A; Mitochondria, Liver; Oxidation-Reduction; Peroxisomes; Rats; Rats, Sprague-Dawley
PubMed: 32493774
DOI: 10.1074/jbc.RA120.013583 -
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 -
Poultry Science Mar 2023CoverCress (low erucic acid, lower fiber pennycress) is being developed as a cover crop to be planted in the fall after corn and harvested in the spring prior to...
CoverCress (low erucic acid, lower fiber pennycress) is being developed as a cover crop to be planted in the fall after corn and harvested in the spring prior to planting soybeans. Two experiments were conducted to evaluate 2 lines of the whole grain (CCWG-1: natural mutation and mutation breeding; CCWG-2: gene edited) and the whole grain pretreated with the potential palatability agent copper sulfate (CCWG-1-CuSO; CCWG-2-CuSO) as an ingredient for broilers. In Experiment 1, CCWG-1-CuSO was included in the diet at 0, 4, and 6% for 41 d. Feed intake, body weight gain, feed conversion, processing characteristics, organ weights, serum thyroid, macropathology and histology data were collected. In Experiment 2, broilers were fed diets containing Control, 2% CCWG-1, 4% CCWG-1, 4% CCWG-2, and 4.35% CCWG-1-CuSO for 42 d. Feed intake, body weight gain, feed conversion, organ weights, serum thyroid, blood chemistries, macropathology, and histology data were collected. In Experiment 1, feed intake and body weight were diminished with no effect on feed conversion for the birds consuming diets containing CCWG-1-CuSO. In Experiment 2, feed intake and body weight were lower with no difference in feed conversion in birds fed diets containing greater than 2% CoverCress grain during d 0 to 28. During d 28 to 42 no difference in feed intake, body weight and an improvement in feed conversion was observed in birds fed all of the CoverCress grain products. In both experiments no significant negative effects were observed in processing, liver, kidney, and thyroid weights, T3, T4, blood chemistries, macropathology, and histopathology between the control and any of the CoverCress grain treatments. No difference in performance was observed in birds fed the mutant (4% CCWG-1) and gene-edited (4% CCWG-2) products. Pretreating CoverCress grain with copper sulfate did not have a significant effect on improving palatability. In conclusion, CoverCress grain can be safely fed to broilers when included at a target rate of 4% in diets and with total glucosinolate levels not to exceed 4.9 µmoles g.
Topics: Animals; Chickens; Copper Sulfate; Plant Breeding; Diet; Body Weight; Animal Feed; Animal Nutritional Physiological Phenomena
PubMed: 36682128
DOI: 10.1016/j.psj.2022.102432