scholarly journals A ‘soft spot’ for drug transport: modulation of cell stiffness using fatty acids and its impact on drug transport in lung model

2015 ◽  
Vol 3 (13) ◽  
pp. 2583-2589 ◽  
Author(s):  
Mehra Haghi ◽  
Daniela Traini ◽  
Lisa G. Wood ◽  
Brian Oliver ◽  
Paul M. Young ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Epithelial Cells ◽  
Drug Transport ◽  
Lung Model ◽  
Cell Stiffness ◽  
Soft Spot ◽  
Transport Modulation ◽  
The Impact

The impact of a polyunsaturated fatty acid, arachidonic acid (AA), on membrane fluidity of epithelial cells and subsequent modulation of the drug transport was investigated.

scholarly journals Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia

2018 ◽  
Vol 19 (11) ◽  
pp. 3325 ◽  
Author(s):  
Lucille Stuani ◽  
Fabien Riols ◽  
Pierre Millard ◽  
Marie Sabatier ◽  
Aurélie Batut ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Acute Myeloid Leukemia ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Myeloid Leukemia ◽  
Metabolic Reprogramming ◽  
Frequent Relapses ◽  
The Impact ◽  
Mutant Cells ◽  
Acute Myeloid

Background: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells. Moreover, two key metabolic enzymes, isocitrate dehydrogenases (IDH1/2), are mutated in more than 15% of AML patient, reinforcing the interest in studying metabolic reprogramming, in particular in this subgroup of patients. Methods: Using a multi-omics approach combining proteomics, lipidomics, and isotopic profiling of [U-13C] glucose and [U-13C] glutamine cultures with more classical biochemical analyses, we studied the impact of the IDH1 R132H mutation in AML cells on lipid biosynthesis. Results: Global proteomic and lipidomic approaches showed a dysregulation of lipid metabolism, especially an increase of phosphatidylinositol, sphingolipids (especially few species of ceramide, sphingosine, and sphinganine), free cholesterol and monounsaturated fatty acids in IDH1 mutant cells. Isotopic profiling of fatty acids revealed that higher lipid anabolism in IDH1 mutant cells corroborated with an increase in lipogenesis fluxes. Conclusions: This integrative approach was efficient to gain insight into metabolism and dynamics of lipid species in leukemic cells. Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production.

scholarly journals Changes in fatty acid levels (saturated, monounsaturated and polyunsaturated) during pregnancy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Estefania Aparicio ◽  
Carla Martín-Grau ◽  
Carmen Hernández-Martinez ◽  
Nuria Voltas ◽  
Josefa Canals ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Docosahexaenoic Acid ◽  
Serum Concentration ◽  
Eicosapentaenoic Acid ◽  
Pregnant Women ◽  
First Trimester ◽  
Third Trimester ◽  
Total N

Abstract Background During pregnancy a high amount of fatty acids (FA) is necessary to meet foetus demands, which vary during gestation. The present study describes the changes in maternal fatty acid concentrations during pregnancy in a sample of pregnant women. Methods This is a longitudinal study of 479 pregnant women who were monitored from the first trimester to third trimester of pregnancy. Data on maternal characteristics were recorded and a serum sample was collected in each trimester. The fatty acid profile (saturated (SFA: total, lauric acid, myristic acid, palmitic acid, stearic acid), monounsaturated (MUFA: total, palmitoleic acid, oleic acid) and polyunsaturated fatty acids (PUFA: total omega-6 (n-6), linoleic acid, dihomo-γ-linolenic acid, arachidonic acid (AA), total omega-3 (n-3), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) was analysed with a gas chromatography-mass spectrometry combination. Results From the first trimester to third trimester of pregnancy, a significant increase in total SFA, total MUFA and total n-6 PUFA was found. (p < 0.001). Nevertheless, the serum concentration of arachidonic acid (AA), eicosapentaenoic acid (EPA) and total n-3 PUFA decreased during gestation (p < 0.001). A statistically non-significant result was observed for the docosahexaenoic acid (DHA) serum concentration between the first and third trimesters of pregnancy. Significant correlations were observed between each total fatty acid concentrations of the first and third trimesters. Conclusion The circulating serum concentration of SFA, MUFA and n-6 PUFA increases during pregnancy, whereas essential fatty acids such as AA and EPA decrease, and DHA remains unchanged. Further research is necessary to understand the role played by FA throughout gestation.

scholarly journals Dietary fat and the diabetic state alter insulin binding and the fatty acyl composition of the adipocyte plasma membrane

1988 ◽  
Vol 253 (2) ◽  
pp. 417-424 ◽  
Author(s):  
C J Field ◽  
E A Ryan ◽  
A B Thomson ◽  
M T Clandinin
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Insulin Binding ◽  
Fatty Acyl ◽  
Membrane Composition ◽  
Membrane Phospholipids ◽  
Diabetic State

Control and diabetic rats were fed on semi-purified high-fat diets providing a polyunsaturated/saturated fatty acid ratio (P/S) of 1.0 or 0.25, to examine the effect of diet on the fatty acid composition of major phospholipids of the adipocyte plasma membrane. Feeding the high-P/S diet (P/S = 1.0) compared with the low-P/S diet (P/S = 0.25) increased the content of polyunsaturated fatty acids in membrane phospholipids in both control and diabetic animals. The diabetic state decreased the content of polyunsaturated fatty acids, particularly arachidonic acid, in adipocyte membrane phospholipids. The decrease in arachidonic acid in membrane phospholipids of diabetic animals tended to be normalized to within the control values when high-P/S diets were given. For control animals, altered plasma-membrane composition was associated with change in insulin binding, suggesting that change in plasma-membrane composition may have physiological consequences for insulin-stimulated functions in the adipocyte.

scholarly journals Mitochondrial-Targeted Antioxidant MitoQ Prevents E. coli Lipopolysaccharide-Induced Accumulation of Triacylglycerol and Lipid Droplets Biogenesis in Epithelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ekaterina Fock ◽  
Vera Bachteeva ◽  
Elena Lavrova ◽  
Rimma Parnova
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Lipid Droplets ◽  
Cellular Respiration ◽  
Mitochondrial Activity ◽  
Energy Regulation ◽  
Metabolic Shift ◽  
Functional Connections ◽  
The Impact

The effect of bacterial lipopolysaccharide (LPS) on eukaryotic cell could be accompanied by a significant metabolic shift that includes accumulation of triacylglycerol (TAG) in lipid droplets (LD), ubiquitous organelles associated with fatty acid storage, energy regulation and demonstrated tight spatial and functional connections with mitochondria. The impairment of mitochondrial activity under pathological stimuli has been shown to provoke TAG storage and LD biogenesis. However the potential mechanisms that link mitochondrial disturbances and TAG accumulation are not completely understood. We hypothesize that mitochondrial ROS (mROS) may play a role of a trigger leading to subsequent accumulation of intracellular TAG and LD in response to a bacterial stimulus. Using isolated epithelial cells from the frog urinary bladder, we showed that LPS decreased fatty acids oxidation, enhanced TAG deposition, and promoted LD formation. LPS treatment did not affect the mitochondrial membrane potential but increased cellular ROS production and led to impairment of mitochondrial function as revealed by decreased ATP production and a reduced maximal oxygen consumption rate (OCR) and OCR directed at ATP turnover. The mitochondrial-targeted antioxidant MitoQ at a dose of 25 nM did not prevent LPS-induced alterations in cellular respiration, but, in contrast to nonmitochondrial antioxidant α-tocopherol, reduced the effect of LPS on the generation of ROS, restored the LPS-induced decline of fatty acids oxidation, and prevented accumulation of TAG and LD biogenesis. The data obtained indicate the key signaling role of mROS in the lipid metabolic shift that occurs under the impact of a bacterial pathogen in epithelial cells.

scholarly journals Impact assessment of the TFA regulation on fatty acid composition of foods in Hungary

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Varga ◽  
E Sarkadi Nagy ◽  
L Zámbó ◽  
É Illés ◽  
M Bakacs ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Trans Fatty Acids ◽  
Saturated Fat ◽  
Portion Size ◽  
World Health ◽  
Food Sources ◽  
Increased Risk ◽  
Total Fat ◽  
The Impact

Abstract Trans fatty acids are formed during the industrial processing of food, and are proven to be harmful for the human body. They have been associated with increased risk of cardiovascular disease, abdominal obesity, diabetes, and certain types of cancer. Decree 71/2013. (XI. 20.) of the Ministry of Human Capacities, which has been in force since 2014, defines the highest permitted amount of trans fats in food products placed on the market in Hungary. The impact of the decree on the industrially produced trans fatty acids (iTFA) availability and population intake was assessed in 2017. Results demonstrated that iTFA were replaced by other fatty acids due to the legislation. In 2019, we investigated food groups which had high measured TFA content before the regulation entered into force and compared the total fat and fatty acid profiles to the same brand or similar products being on the market afterwards. In collaboration with the World Health Organization, this was the first assessment to determine to which extent manufacturers increased saturated fat (SFA) content of foodstuffs to reduce iTFA content. In those product groups, which were identified as significant food sources of iTFA before introducing the regulation (biscuits, coffee creamers and flavorings, sweets, bakery products, confectionary, wafers, margarines) we found no significant changes in the total fat content, while in most foodstuffs the average proportion of SFA was higher after reformulation, as iTFA were mainly substituted with SFA in 61% of the products, with cis-MUFA in 25% and cis-PUFA in 14% of the products, respectively. Evidence from this analysis supports concerns that eliminating iTFA in certain foodstuffs leads to unwanted substitution with saturated fat, hence reducing the possible health benefits. Given the high SFA intake and the unfavourable cardiovascular statistics in Hungary, the consumption frequency and portion size control of these products are advised. Key messages Monitoring the changes of food composition is important in order to evaluate the effect of the regulation. Manufacturers should be encouraged to reduce the SFA content to a technologically feasible level.

Fatty acid profiles of intramuscular, intermuscular, external and internal fat in Polish Holstein-Friesian × Hereford bulls and steers fed grass silage-based diets supplemented with concentrates

2017 ◽  
Vol 57 (2) ◽  
pp. 371 ◽  
Author(s):  
Zofia Wielgosz-Groth ◽  
Monika Sobczuk-Szul ◽  
Zenon Nogalski ◽  
Magdalena Mochol ◽  
Cezary Purwin ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Energy Requirement ◽  
Net Energy ◽  
Feeding Intensity ◽  
Fat Depots ◽  
Grass Silage ◽  
Fat Deposits ◽  
Holstein Friesian ◽  
The Impact

This paper determined the impact of gender and feeding intensity on the profile of fatty acids in different types of fat deposits. The studies were conducted with 20 young bulls and 20 steers, which were Polish Holstein-Friesian and Hereford crossbreds fattened intensively – grass silage ad libitum and concentrate covered 50% of the net energy requirement in fattened cattle or semi-intensively – concentrate covered 30% of the net energy. The fatty acid profile in intramuscular, intermuscular, external and internal fat was determined. The content of intramuscular fat was lower (P < 0.001) in the longissimus muscle in the bulls (1.74%) than in the steers (3.71%). In fat of steers, the proportion of monounsaturated fatty acids was higher whereas in fat of bulls, the content of polyunsaturated fatty acids was higher. Generally the impact of the location of fat depots on the profile of fatty acids was statistically significant (P < 0.001) but there was no effect of feeding intensity.

scholarly journals Porcine Hepatic Response to Fumonisin B1 in a Short Exposure Period: Fatty Acid Profile and Clinical Investigations

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 655 ◽  
Author(s):  
Omeralfaroug Ali ◽  
Judit Szabó-Fodor ◽  
Hedvig Fébel ◽  
Miklós Mézes ◽  
Krisztián Balogh ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acids ◽  
Fumonisin B1 ◽  
Exposure Period ◽  
Short Exposure ◽  
Lung Edema ◽  
Fungal Culture ◽  
Arachidonic Acids ◽  
The Impact

Scarce studies have investigated the impact of fumonisin B1 (FB1) on the hepatic tissue fatty acid (FA) profile, and no study is available on piglets. A 10-day in vivo experiment was performed on seven piglets/group: control and FB1-fed animals (diet was contaminated with fungal culture: 20 mg FB1/kg diet). Independent sample t-test was carried out at p < 0.05 as the significance level. Neither growth, nor feed efficiency, was affected. The hepatic phospholipid (PL) fatty acids (FAs) were more susceptible for FB1, while triglyceride (TG) was less responsive. The impact of FB1 on hepatic PL polyunsaturated fatty acids (PUFAs) was more pronounced than on saturated fatty acids. Among all PUFAs, predominant ones in response were docosapentaenoicacid (DPA) (↓), docosahexaenoic DHA (↓) and arachidonic acids (↑). This led to a higher omega-6:omega-3 ratio, whereas a similar finding was noted in TGs. Neither total saturation (SFA) nor total monousaturation (MUFA) were affected by the FB1 administration. The liver showed an increase in malondialdehyde, as well as antioxidant capacity (reduced glutathione and glutathione peroxidase). The plasma enzymatic assessment revealed an increase in alkaline phosphatase (ALP), while alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) were not influenced. The microscopic sections provided evidence of vacuolar degeneration of the hepatocytes’ cytoplasm, but it was not severe. Furthermore, the lung edema was developed, while the kidney was not affected. In conclusion, regarding FB1-mediated hepatotoxicity in piglets, the potential effect of slight hepatotoxicity did not compromise growth performance, at least at the dose and exposure period applied.

scholarly journals Exposure to a Farm Environment During Pregnancy Increases the Proportion of Arachidonic Acid in the Cord Sera of Offspring

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 238 ◽  
Author(s):  
Malin Barman ◽  
Karin Jonsson ◽  
Agnes E. Wold ◽  
Ann-Sofie Sandberg
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Breast Milk ◽  
Acid Composition ◽  
Post Partum ◽  
Maternal Diet ◽  
Circulation System ◽  
Adrenic Acid

Growing up in a farm environment is protective against allergy development. Various explanations have been put forward to explain this association. Fatty acids are regulators of immune function and the composition of fatty acids in the circulation system may affect immune development. Here, we investigate whether the fatty acid composition of cord serum differs for infants born to Farm (n = 26) or non-Farm mothers (n =29) in the FARMFLORA birth-cohort. For comparison, the levels of fatty acids in the maternal diet, serum and breast milk around 1 month post-partum were recorded. The fatty acids in the cord sera from infants born to Farm mothers had higher proportions of arachidonic acid (20:4 n-6) and adrenic acid (22:4 n-6) than those from infants born to non-Farm mothers. No differences were found for either arachidonic acid or adrenic acid in the diet, samples of the serum, or breast milk from Farm and non-Farm mothers obtained around 1 month post-partum. The arachidonic and adrenic acid levels in the cord blood were unrelated to allergy outcome for the infants. The results suggest that a farm environment may be associated with the fatty acid composition to which the fetus is exposed during pregnancy.

Free fatty acid metabolism in aerobically fit individuals

1994 ◽  
Vol 77 (5) ◽  
pp. 2374-2379 ◽  
Author(s):  
J. Calles-Escandon ◽  
P. Driscoll
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Aerobic Fitness ◽  
Fat Free Mass ◽  
Acid Oxidation ◽  
Systemic Delivery ◽  
Maximal Aerobic Capacity ◽  
Fitness Level ◽  
The Impact

The impact of aerobic fitness level on the production and disposal of serum free fatty acids was investigated in 26 normal young volunteers. The fitness level was ascertained by history and confirmed by determination of maximal aerobic capacity. Energy expenditure and substrate oxidation at rest were measured with indirect calorimetry. Free fatty acid turnover was measured with an infusion of [14C]palmitic acid. All tests were done > or = 48 h after the last bout of exercise. The sedentary (SED) volunteers had higher rates of systemic delivery of fatty acids than aerobically fit (FIT) individuals (532 +/- 53.4 vs. 353 +/- 62.3 mumol/min; P = 0.05). This difference was accentuated when the values were normalized to fat-free mass (9.2 +/- 0.8 and 5.9 +/- 0.98 mumol.kg-1.min-1 for SED and FIT, respectively). Fatty acid oxidation was similar between FIT and SED volunteers in absolute numbers (209 +/- 25 vs. 202 +/- 21 mumol/min, respectively; NS) as well as when normalized to fat-free mass (3.8 +/- 0.9 vs. 3.6 +/- 1.4 mumol.kg-1.min-1, respectively; NS). In contrast, the nonoxidative disposal of serum fatty acids was higher in SED (330 +/- 46.1 mumol/min) than in FIT individuals (144 +/- 52 mumol/min; P = 0.026). Thus, the ratio of nonoxidative to oxidative disposal rates of fatty acids was higher in SED than in FIT individuals (1.65 +/- 0.29 vs. 0.75 +/- 0.17; P = 0.021). The data support the hypothesis that high aerobic fitness level is associated with a low rate of systemic delivery of fatty acids at rest. Nevertheless, subjects with high aerobic fitness levels have fat oxidation at the same rate as unfit individuals.

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