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The Journal of Nutrition Jun 2020The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus,...
BACKGROUND
The cognitive impairments that characterize Down syndrome (DS) have been attributed to brain hypocellularity due to neurogenesis impairment during fetal stages. Thus, enhancing prenatal neurogenesis in DS could prevent or reduce some of the neuromorphological and cognitive defects found in postnatal stages.
OBJECTIVES
As fatty acids play a fundamental role in morphogenesis and brain development during fetal stages, in this study, we aimed to enhance neurogenesis and the cognitive abilities of the Ts65Dn (TS) mouse model of DS by administering oleic or linolenic acid.
METHODS
In total, 85 pregnant TS females were subcutaneously treated from Embryonic Day (ED) 10 until Postnatal Day (PD) 2 with oleic acid (400 mg/kg), linolenic acid (500 mg/kg), or vehicle. All analyses were performed on their TS and Control (CO) male and female progeny. At PD2, we evaluated the short-term effects of the treatments on neurogenesis, cellularity, and brain weight, in 40 TS and CO pups. A total of 69 TS and CO mice were used to test the long-term effects of the prenatal treatments on cognition from PD30 to PD45, and on neurogenesis, cellularity, and synaptic markers, at PD45. Data were compared by ANOVAs.
RESULTS
Prenatal administration of oleic or linolenic acid increased the brain weight (+36.7% and +45%, P < 0.01), the density of BrdU (bromodeoxyuridine)- (+80% and +115%; P < 0.01), and DAPI (4',6-diamidino-2-phenylindole)-positive cells (+64% and +22%, P < 0.05) of PD2 TS mice with respect to the vehicle-treated TS mice. Between PD30 and PD45, TS mice prenatally treated with oleic or linolenic acid showed better cognitive abilities (+28% and +25%, P < 0.01) and a higher density of the postsynaptic marker PSD95 (postsynaptic density protein 95) (+65% and +44%, P < 0.05) than the vehicle-treated TS animals.
CONCLUSION
The beneficial cognitive and neuromorphological effects induced by oleic or linolenic acid in TS mice suggest that they could be promising pharmacotherapies for DS-associated cognitive deficits.
Topics: Animals; Body Weight; Brain; Cognition; Disease Models, Animal; Down Syndrome; Female; Maternal Exposure; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Neurogenesis; Oleic Acid; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; alpha-Linolenic Acid
PubMed: 32243527
DOI: 10.1093/jn/nxaa074 -
Molecular Biology and Evolution Nov 2020A challenging question in evolutionary theory is the origin of cell division and plausible molecular mechanisms involved. Here, we made the surprising observation that...
A challenging question in evolutionary theory is the origin of cell division and plausible molecular mechanisms involved. Here, we made the surprising observation that complexes formed by short alpha-helical peptides and oleic acid can create multiple membrane-enclosed spaces from a single lipid vesicle. The findings suggest that such complexes may contain the molecular information necessary to initiate and sustain this process. Based on these observations, we propose a new molecular model to understand protocell division.
Topics: Artificial Cells; Cell Division; Cytoplasmic Vesicles; Lactalbumin; Membranes; Oleic Acid; Peptides
PubMed: 32521018
DOI: 10.1093/molbev/msaa138 -
Journal of Dairy Science Feb 2024The concept that fat supplementation impairs total-tract fiber digestibility in ruminants has been widely accepted over the past decades. Nevertheless, the recent...
The concept that fat supplementation impairs total-tract fiber digestibility in ruminants has been widely accepted over the past decades. Nevertheless, the recent interest in the dietary fatty acid profile to dairy cows enlightened the possible beneficial effect of specific fatty acids (e.g., palmitic, stearic, and oleic acids) on total-tract fiber digestibility. Because palmitic, stearic, and oleic acids are the main fatty acids present in ruminal bacterial cells, we hypothesize that the dietary supply of these fatty acids will favor their incorporation into the bacterial cell membranes, which will support the growth and enrichment of fiber-digesting bacteria in the rumen. Our objective in this experiment was to investigate how dietary supply of palmitic, stearic, and oleic acid affect fiber digestion, bacterial membrane fatty acid profile, microbial growth, and composition of the rumen bacterial community. Diets were randomly assigned to 8 single-flow continuous culture fermenters arranged in a replicated 4 × 4 Latin square with four 11-d experimental periods. Treatments were (1) a control basal diet without supplemental fatty acids (CON); (2) the control diet plus palmitic acid (PA); (3) the control diet plus stearic acid (SA); and (4) the control diet plus oleic acid (OA). All fatty acid treatments were included in the diet at 1.5% of the diet (dry matter [DM] basis). The basal diet contained 50% orchardgrass hay and 50% concentrate (DM basis) and was supplied at a rate of 60 g of DM/d in 2 equal daily offers (0800 and 1600 h). Data were analyzed using a mixed model considering treatments as fixed effect and period and fermenter as random effects. Our results indicate that PA increased in vitro fiber digestibility by 6 percentage units compared with the CON, while SA had no effect and OA decreased fiber digestibility by 8 percentage units. Oleic acid decreased protein expression of the enzymes acetyl-CoA carboxylase compared with CON and PA, while fatty acid synthase was reduced by PA, SA, and OA. We observed that PA, but not SA or OA, altered the bacterial community composition by enhancing bacterial groups responsible for fiber digestion. Although the dietary fatty acids did not affect the total lipid content and the phospholipid fraction in the bacterial cell, PA increased the flow of anteiso C13:0 and anteiso C15:0 in the phospholipidic membrane compared to the other treatments. In addition, OA increased the flow of C18:1 cis-9 and decreased C18:2 cis-9,cis-12 in the bacterial phospholipidic membranes compared to the other treatments. Palmitic acid tended to increase bacterial growth compared to other treatments, whereas SA and OA did not affect bacterial growth compared with CON. To our knowledge, this is the first research providing evidence that palmitic acid supports ruminal fiber digestion through shifts in bacterial fatty acid metabolism that result in changes in growth and abundance of fiber-degrading bacteria in the microbial community.
Topics: Cattle; Female; Animals; Oleic Acid; Dietary Supplements; Milk; Lactation; Rumen; Digestion; Fatty Acids; Diet; Palmitic Acid
PubMed: 37776997
DOI: 10.3168/jds.2023-23568 -
ACS Synthetic Biology Apr 2022Oleic acid is widely applied in the chemical, material, nutritional, and pharmaceutical industries. However, the current production of oleic acid via high oleic plant...
Oleic acid is widely applied in the chemical, material, nutritional, and pharmaceutical industries. However, the current production of oleic acid via high oleic plant oils is limited by the long growth cycle and climatic constraints. Moreover, the global demand for high oleic plant oils, especially the palm oil, has emerged as the driver of tropical deforestation causing tropical rainforest destruction, climate change, and biodiversity loss. In the present study, an alternative and sustainable strategy for high oleic oil production was established by reprogramming the metabolism of the oleaginous yeast using a two-layer "push-pull-block" strategy. Specifically, the fatty acid synthesis pathway was first engineered to increase oleic acid proportion by altering the fatty acid profiles. Then, the content of storage oils containing oleic acid was boosted by engineering the synthesis and degradation pathways of triacylglycerides. The strain resulting from this two-layer engineering strategy produced the highest titer of high oleic microbial oil reaching 56 g/L with 84% oleic acid in fed-batch fermentation, representing a remarkable improvement of a 110-fold oil titer and 2.24-fold oleic acid proportion compared with the starting strain. This alternative and sustainable method for high oleic oil production shows the potential of substitute planting.
Topics: Fatty Acids; Metabolic Engineering; Oleic Acid; Plant Oils; Yarrowia
PubMed: 35311250
DOI: 10.1021/acssynbio.1c00613 -
Poultry Science Jan 2023Hepatic steatosis is a highly prevalent liver disease, yet research on it is hampered by the lack of tractable cellular models in poultry. To examine the possibility of...
Hepatic steatosis is a highly prevalent liver disease, yet research on it is hampered by the lack of tractable cellular models in poultry. To examine the possibility of using organoids to model steatosis and detect it efficiently in leghorn male hepatocellular (LMH) cells, we first established steatosis using different concentrations of oleic acid (OA) (0.05-0.75 mmol/L) for 12 or 24 h. The subsequent detections found that the treatment of LMH cells with OA resulted in a dramatic increase in intracellular triglyceride (TG) concentrations, which was positively associated with the concentration of the inducing OA (R > 0.9). Then, the modeled steatosis was detected by flow cytometry after NileRed staining and it was found that the intensity of NileRed-A was positively correlated with the TG concentration (R > 0.93), which demonstrates that the flow cytometry is suitable for the detection of steatosis in LMH cells. According to the detection results of the different steatosis models, we confirmed that the optimal induction condition for the establishment of the steatosis model in LMH cells is OA (0.375 mmol/L) incubation for 12 h. Finally, the transcription and protein content of fat metabolism-related genes in steatosis model cells were detected. It was found that OA-induced steatosis could significantly decrease the expression of nuclear receptor PPAR-γ and the synthesis of fatty acids (SREBP-1C, ACC1, FASN), increasing the oxidative decomposition of triglycerides (CPT1A) and the assembly of low-density lipoproteins (MTTP, ApoB). Sterol metabolism in model cells was also significantly enhanced (HMGR, ABCA1, L-BABP). This study established, detected, and analyzed an OA-induced steatosis model in LMH cells, which provides a stable model and detection method for the study of poultry steatosis-related diseases.
Topics: Male; Animals; Oleic Acid; Lipid Metabolism; Chickens; Fatty Liver; Fatty Acids; Liver
PubMed: 36446267
DOI: 10.1016/j.psj.2022.102297 -
Nutrients Sep 2019The consumption of an olive oil rich diet has been associated with the diminished incidence of cardiovascular disease and cancer. Several studies have attributed these... (Review)
Review
The consumption of an olive oil rich diet has been associated with the diminished incidence of cardiovascular disease and cancer. Several studies have attributed these beneficial effects to oleic acid (C18 n-9), the predominant fatty acid principal component of olive oil. Oleic acid is not an essential fatty acid since it can be endogenously synthesized in humans. Stearoyl-CoA desaturase 1 (SCD1) is the enzyme responsible for oleic acid production and, more generally, for the synthesis of monounsaturated fatty acids (MUFA). The saturated to monounsaturated fatty acid ratio affects the regulation of cell growth and differentiation, and alteration in this ratio has been implicated in a variety of diseases, such as liver dysfunction and intestinal inflammation. In this review, we discuss our current understanding of the impact of gene-nutrient interactions in liver and gut diseases, by taking advantage of the role of SCD1 and its product oleic acid in the modulation of different hepatic and intestinal metabolic pathways.
Topics: Diet; Gastrointestinal Tract; Humans; Liver; Oleic Acid; Stearoyl-CoA Desaturase
PubMed: 31554181
DOI: 10.3390/nu11102283 -
Adipocyte Dec 2022Metabolic disorders related to obesity are largely dependent on adipose tissue hypertrophy, which involves adipocyte hypertrophy and increased adipogenesis. Adiposize is...
Metabolic disorders related to obesity are largely dependent on adipose tissue hypertrophy, which involves adipocyte hypertrophy and increased adipogenesis. Adiposize is regulated by lipid accumulation as a result of increased lipogenesis (mainly lipid uptake in mature adipocytes) and reduced lipolysis. Using realtime 2D cell culture analyses of lipid uptake, we show (1) that high glucose concentration (4.5 g/L) was required to accumulate oleic acid increasing lipid droplet size until unilocularization similar to mature adipocytes in few days, (2) oleic acid reduced ( gene transcription and (3) insulin counteracted oleic acid-induced increase of lipid droplet size. Although the lipolytic activity observed in high low glucose (1 g/L) conditions was not altered, insulin was found to inhibit oleic acid induced gene transcription required for lipid storage such as Cell Death Inducing DFFA Like Effectors (CIDEC) and G0 switch gene S2), possibly through PPARA activity. Although this signalling pathway requires more detailed investigation, the results point out the differential mechanisms involved in the pro-adipogenic effect of insulin in absence its protective effect on adiposity in presence of oleic acid uptake.: AICAR, 5-Aminoimidazole-4-carboxamide-1-D-ribofuranoside; AMPK, AMP-Activated protein kinase, ASCs, adipose stem cell; ATGL, adipose triglyceride lipase; BSA, Bovine serum albumin; CEBPA, CCAAT enhancer binding protein alpha; CIDEs, Cell Death Inducing DFFA Like Effectors; dA, differentiated adipocyte; DMEM, Dulbecco's Modified Eagle's Medium; FABPs, Fatty Acid Binding Proteins; FAT/CD36, Fatty acid translocase; FCS, Foetal calf serum; FN1, fibronectin 1; FFA, free fatty acid; G0S2, G0 switch gene S2; GLUTs, Glucose transporters; GPR120, G protein-coupled receptor 120; HG, high glucose; HSL, hormone sensitive lipase; INSR, insulin receptor; LG, low glucose; OA, oleic acid; PBS, Phosphate buffer saline; PPARs, Peroxisome-Proliferator Activated Receptors; PKA, Protein kinase cyclic AMP-dependent; PKG, Protein kinase cyclic GMP dependent; PTGS2, cytochrome oxidase 2; RTCA, realtime cell analysis; TG, triglyceride.
Topics: Adipocytes; Fatty Acids; Glucose; Humans; Hypertrophy; Insulin; Lipolysis; Obesity; Oleic Acid; Protein Kinases
PubMed: 35946137
DOI: 10.1080/21623945.2022.2107784 -
Critical Reviews in Food Science and... 2022The aim of this systematic review and meta-analysis was to analyze data from randomized controlled trials (RCTs) assessing the effects of oleic acid (OA) supplementation... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review and meta-analysis was to analyze data from randomized controlled trials (RCTs) assessing the effects of oleic acid (OA) supplementation on blood inflammatory markers in adults. PubMed, EMBASE and Cochrane Library databases were systematically searched from 1950 to 2019, with adults and a minimum intervention duration of 4 weeks. The effect size was estimated, adopting standardized mean difference (SMD) and 95% confidence interval (CI). Of the 719 identified studies, thirty-one RCTs involving 1634 subjects were eligible. The results of this study revealed that increasing OA supplementation significantly reduced C-reactive protein (CRP) (SMD: -0.11, 95% CI: -0.21, -0.01, P = 0.038). However, dietary OA consumption did not significantly affect tumor necrosis factor (TNF) (SMD: -0.05, 95% CI: -0.19, 0.10, P = 0.534), interleukin 6 (IL-6) (SMD: 0.01, 95% CI: -0.10, 0.13, P = 0.849), fibrinogen (SMD: 0.08, 95% CI: -0.16, 0.31, P = 0.520), plasminogen activator inhibitor type 1 (PAI-1) activity (SMD: -0.11, 95% CI: -0.34, 0.12, P = 0.355), soluble intercellular adhesion molecule-1 (sICAM-1) (SMD: -0.06, 95% CI: -0.26, 0.13, P = 0.595) or soluble vascular cell adhesion molecule-1 (sVCAM-1) (SMD: -0.04, 95% CI: -0.27, 0.18, P = 0.701). Overall, the meta-analysis demonstrated that dietary OA supplementation significantly reduced CRP, yet did not affect other inflammatory markers including TNF, IL-6, fibrinogen, PAI-1 activity, sICAM-1or sVCAM-1.
Topics: Biomarkers; Dietary Supplements; Humans; Inflammation; Oleic Acid; Randomized Controlled Trials as Topic
PubMed: 33305589
DOI: 10.1080/10408398.2020.1854673 -
Archives of Toxicology Jun 2023Intestinal cells are continuously exposed to food constituents while adapting to peristaltic movement and fluid shear stress. Oleic acid (OA) and palmitic acid (PA) are...
Intestinal cells are continuously exposed to food constituents while adapting to peristaltic movement and fluid shear stress. Oleic acid (OA) and palmitic acid (PA) are among the most prevalent fatty acids with respect to dietary lipids. Despite the central importance of dietary lipids for a balanced diet, awareness about potential detrimental effects related to excessive consumption is increasing; this includes toxicity, metabolic deregulation, and, particularly for cancer cells, a benefit from the uptake of fatty acids related to promotion of metastasis. Expanding on this, we started elucidating the effects of OA and PA (25-500 µM) on non-transformed human intestinal epithelial cells (HCEC-1CT) in comparison to colon carcinoma cells (HCT116), with regard to the mechanosensory apparatus. Hence, intestinal cells' motility is on the one side essential to ensure adaption to peristaltic movement and barrier function, but also to enable metastatic progression. Incubation with both OA and PA (≥ 25 µM) significantly decreased membrane fluidity of HCT116 cells, whereas the effect on HCEC-1CT was more limited. Application of rhodamine-labelled PA demonstrated that the fatty acid is incorporated into the plasma membrane of HCT116, which could not be observed in the non-tumorigenic cell line. Down-streaming into the intracellular compartment, a pronounced rearrangement of actin cytoskeleton was evident in both cell lines (OA and PA; 25 and 100 µM). This was accompanied by a variation of translocation efficiency of the mechanosensitive co-transcription factor YAP1, albeit with a stronger effect seen for PA and the cancer cells. Untargeted proteomic analysis confirmed that exposure to OA and PA could alter the response capacity of HCT116 cells to fluid shear stress. Taken together, OA and PA were able to functionally modulate the mechanosensory apparatus of intestinal cells, implying a novel role for dietary fatty acids in the regulation of intestinal pathophysiology.
Topics: Humans; Palmitic Acid; Mechanotransduction, Cellular; Proteomics; Fatty Acids; Oleic Acid
PubMed: 37117602
DOI: 10.1007/s00204-023-03495-3 -
European Biophysics Journal : EBJ Jan 2022Human serum albumin binds a wide variety of drugs with different structure and affinity to two main binding sites, drug site 1 (DS1) and drug site 2 (DS2), which...
Human serum albumin binds a wide variety of drugs with different structure and affinity to two main binding sites, drug site 1 (DS1) and drug site 2 (DS2), which partially or totally overlap with fatty acid (FA) sites. Although multiple binding sites are available for endogenous compounds, FAs are the primary physiological ligands of albumin and their competition in the occupancy of DS1 and DS2 affects the binding of exogenous molecules, with a possible impact on drug delivery. In this work, we have investigated the simultaneous binding of oleic acid, warfarin and ibuprofen to albumin using differential scanning calorimetry and fluorescence to evaluate the impact on the conformational stability of the protein. The two drugs are widely used for their anticoagulant (warfarin) and anti-inflammatory (ibuprofen) properties, and can be also considered as site markers to probe DS1 and DS2, respectively. Oleic acid is one of the most important fatty acids from a physiological point of view for its role as a source of energy for cells, and also it binds albumin with the highest association constant. When complexed with oleic acid the calorimetric profile of albumin shows a biphasic trend whose line shape depends on the ligand concentration. The binding capacity of either warfarin or ibuprofen to albumin is modulated by oleate molecules in a concentration-dependent mode being synergic cooperative (warfarin) or competitive-like (ibuprofen). The overall results provide insights on the dynamics of albumin/ligands complex, which in turn may have important pharmacokinetic and pharmacodynamic implications.
Topics: Binding Sites; Humans; Ibuprofen; Oleic Acid; Protein Binding; Serum Albumin, Human; Warfarin
PubMed: 35048131
DOI: 10.1007/s00249-021-01582-w