Publications by authors named "Eric Mignolet"

22 Publications

  • Page 1 of 1

Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells.

Nutrients 2021 Aug 10;13(8). Epub 2021 Aug 10.

Louvain Institute of Biomolecular Science and Technology (LIBST), UCLouvain, Croix du Sud 4-5/L7.07.03, B-1348 Louvain-la-Neuve, Belgium.

Plant-derived conjugated linolenic acids (CLnA) have been widely studied for their preventive and therapeutic properties against diverse diseases such as cancer. In particular, punicic acid (PunA), a conjugated linolenic acid isomer (C18:3 c9t11c13) present at up to 83% in pomegranate seed oil, has been shown to exert anti-cancer effects, although the mechanism behind its cytotoxicity remains unclear. Ferroptosis, a cell death triggered by an overwhelming accumulation of lipid peroxides, has recently arisen as a potential mechanism underlying CLnA cytotoxicity. In the present study, we show that PunA is highly cytotoxic to HCT-116 colorectal and FaDu hypopharyngeal carcinoma cells grown either in monolayers or as three-dimensional spheroids. Moreover, our data indicate that PunA triggers ferroptosis in carcinoma cells. It induces significant lipid peroxidation and its effects are prevented by the addition of ferroptosis inhibitors. A combination with docosahexaenoic acid (DHA), a known polyunsaturated fatty acid with anticancer properties, synergistically increases PunA cytotoxicity. Our findings highlight the potential of using PunA as a ferroptosis-sensitizing phytochemical for the prevention and treatment of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13082751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399984PMC
August 2021

Green Tea Extract Enhances the Oxidative Stability of DHA-Rich Oil.

Antioxidants (Basel) 2021 Jun 19;10(6). Epub 2021 Jun 19.

Louvain Institute of Biomolecular Science and Technology, UCLouvain, Croix du Sud, 4-5, L7.07.03, B-1348 Louvain-la-Neuve, Belgium.

Docosahexaenoic acid (DHA) is one of the most important omega-3 polyunsaturated fatty acids, with proven health-promoting properties. However, oils with a very high content in DHA (DHAO) are extremely susceptible to oxidation, which affects shelf stability and limits incorporation in food products. Green tea extracts (GTE) are potential candidates for the protection of these oils, but their use in such oils has not been previously reported. This study investigated the effect of GTE (160 ppm, 400 ppm, 1000 ppm) and α-tocopherol (80 ppm, 200 ppm, 500 ppm) on the oxidative stability of a DHAO over a 9-week storage at 30 °C. The oxidative status was monitored during storage by the measurement of peroxide value (PV) and -anisidine value (-AV). Changes in eicosapentaenoic acid (EPA) and DHA content, as well as in catechins and tocopherol contents, were also evaluated. The addition of GTE enhanced the oxidative stability of DHAO by reducing the formation of peroxides and secondary oxidation products, whereas α-tocopherol had no significant effect on the PV of oil during storage but led to a significantly higher -AV. The EPA and DHA content of DHAO was stable in GTE-supplemented samples whereas a decrease was observed in the control and α-tocopherol-supplemented samples. GTE also delayed the degradation of tocopherols initially present in the oil, while catechins resulting from the addition of GTE decreased progressively during the storage period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10060982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235633PMC
June 2021

Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects.

Cell Metab 2021 Aug 11;33(8):1701-1715.e5. Epub 2021 Jun 11.

Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, 57 Avenue Hippocrate B1.5704, 1200 Brussels, Belgium. Electronic address:

Tumor acidosis promotes disease progression through a stimulation of fatty acid (FA) metabolism in cancer cells. Instead of blocking the use of FAs by acidic cancer cells, we examined whether excess uptake of specific FAs could lead to antitumor effects. We found that n-3 but also remarkably n-6 polyunsaturated FA (PUFA) selectively induced ferroptosis in cancer cells under ambient acidosis. Upon exceeding buffering capacity of triglyceride storage into lipid droplets, n-3 and n-6 PUFA peroxidation led to cytotoxic effects in proportion to the number of double bonds and even more so in the presence of diacylglycerol acyltransferase inhibitors (DGATi). Finally, an n-3 long-chain PUFA-rich diet significantly delayed mouse tumor growth when compared with a monounsaturated FA-rich diet, an effect further accentuated by administration of DGATi or ferroptosis inducers. These data point out dietary PUFA as a selective adjuvant antitumor modality that may efficiently complement pharmacological approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2021.05.016DOI Listing
August 2021

The Egg Yolk Content in ω-3 and Conjugated Fatty Acids Can Be Sustainably Increased upon Long-Term Feeding of Laying Hens with a Diet Containing Flaxseeds and Pomegranate Seed Oil.

Foods 2021 May 19;10(5). Epub 2021 May 19.

Louvain Institute of Biomolecular Science and Technology, UCLouvain, 1348 Louvain-la-Neuve, Belgium.

Long-term feeding trials examining the incorporation of conjugated linolenic acids (CLnA) into the diet of laying hens are lacking. In the present study, we compared two diets in sixty-six red Sex-Link hens (33 hens/treatment), fed for 26 weeks. The control diet was high in oleic acid, while the test diet was high in α-linolenic acid (ALA) and punicic acid (PunA). No significant differences were observed between treatments for hens' performance, egg weight and yolk weight. In contrast, dietary ALA and PunA resulted in a significant increase in n-3 PUFA, rumenic acid (RmA) and PunA contents in egg yolk, as well as in the liver, heart, muscle and adipose tissue of the hens. Other conjugated dienes resulting from the metabolism of PunA or RmA also accumulated in the egg yolk and tissues. Unlike DHA, which was exclusively distributed in phospholipids, ALA, RmA and PunA were preferably distributed in triglycerides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods10051134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160806PMC
May 2021

Impaired Cytoskeletal and Membrane Biophysical Properties of Acanthocytes in Hypobetalipoproteinemia - A Case Study.

Front Physiol 2021 23;12:638027. Epub 2021 Feb 23.

CELL Unit & PICT Imaging Platform, de Duve Institute, UCLouvain, Brussels, Belgium.

Familial hypobetalipoproteinemia is a metabolic disorder mainly caused by mutations in the gene. In its homozygous form it can lead without treatment to severe ophthalmological and neurological manifestations. In contrast, the heterozygous form is generally asymptomatic but associated with a low risk of cardiovascular disease. Acanthocytes or thorny red blood cells (RBCs) are described for both forms of the disease. However, those morphological changes are poorly characterized and their potential consequences for RBC functionality are not understood. Thus, in the present study, we asked whether, to what extent and how acanthocytes from a patient with heterozygous familial hypobetalipoproteinemia could exhibit altered RBC functionality. Acanthocytes represented 50% of the total RBC population and contained mitoTracker-positive surface patches, indicating the presence of mitochondrial fragments. While RBC osmotic fragility, calcium content and ATP homeostasis were preserved, a slight decrease of RBC deformability combined with an increase of intracellular free reactive oxygen species were observed. The spectrin cytoskeleton was altered, showing a lower density and an enrichment in patches. At the membrane level, no obvious modification of the RBC membrane fatty acids nor of the cholesterol content were detected but the ceramide species were all increased. Membrane stiffness and curvature were also increased whereas transversal asymmetry was preserved. In contrast, lateral asymmetry was highly impaired showing: (i) increased abundance and decreased functionality of sphingomyelin-enriched domains; (ii) cholesterol enrichment in spicules; and (iii) ceramide enrichment in patches. We propose that oxidative stress induces cytoskeletal alterations, leading to increased membrane stiffness and curvature and impaired lipid lateral distribution in domains and spicules. In addition, ceramide- and spectrin-enriched patches could result from a RBC maturation defect. Altogether, the data indicate that acanthocytes are associated with cytoskeletal and membrane lipid lateral asymmetry alterations, while deformability is only mildly impaired. In addition, familial hypobetalipoproteinemia might also affect RBC precursors leading to disturbed RBC maturation. This study paves the way for the potential use of membrane biophysics and lipid vital imaging as new methods for diagnosis of RBC disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.638027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940373PMC
February 2021

A Three-Month Consumption of Eggs Enriched with ω-3, ω-5 and ω-7 Polyunsaturated Fatty Acids Significantly Decreases the Waist Circumference of Subjects at Risk of Developing Metabolic Syndrome: A Double-Blind Randomized Controlled Trial.

Nutrients 2021 Feb 18;13(2). Epub 2021 Feb 18.

Louvain Institute of Biomolecular Science and Technology, UCLouvain, 1348 Louvain-la-Neuve, Belgium.

Alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), rumenic acid (RmA), and punicic acid (PunA) are claimed to influence several physiological functions including insulin sensitivity, lipid metabolism and inflammatory processes. In this double-blind randomized controlled trial, we investigated the combined effect of ALA, DHA, RmA and PunA on subjects at risk of developing metabolic syndrome. Twenty-four women and men were randomly assigned to two groups. Each day, they consumed two eggs enriched with oleic acid (control group) or enriched with ALA, DHA, RmA, and PunA (test group) for 3 months. The waist circumference decreased significantly (-3.17 cm; < 0.001) in the test group. There were no major changes in plasma insulin and blood glucose in the two groups. The dietary treatments had no significant effect on endothelial function as measured by peripheral arterial tonometry, although erythrocyte nitrosylated hemoglobin concentrations tended to decrease. The high consumption of eggs induced significant elevations in plasma low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol ( < 0.001), which did not result in any change in the LDL/HDL ratio in both groups. These results indicate that consumption of eggs enriched with ALA, DHA, RmA and PunA resulted in favorable changes in abdominal obesity without affecting other factors of the metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13020663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923083PMC
February 2021

Interplay Between Plasma Membrane Lipid Alteration, Oxidative Stress and Calcium-Based Mechanism for Extracellular Vesicle Biogenesis From Erythrocytes During Blood Storage.

Front Physiol 2020 3;11:712. Epub 2020 Jul 3.

CELL Unit and PICT Platform, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.

The shedding of extracellular vesicles (EVs) from the red blood cell (RBC) surface is observed during senescence and RBC storage . Two main models for EV shedding, respectively based on calcium rise and oxidative stress, have been proposed in the literature but the role of the plasma membrane lipid composition and properties is not understood. Using blood in K/EDTA tubes stored for up to 4 weeks at 4°C as a relevant RBC vesiculation model, we showed here that the RBC plasma membrane lipid composition, organization in domains and biophysical properties were progressively modified during storage and contributed to the RBC vesiculation. First, the membrane content in cholesterol and linoleic acid decreased whereas lipid peroxidation and spectrin:membrane occupancy increased, all compatible with higher membrane rigidity. Second, phosphatidylserine surface exposure showed a first rapid rise due to membrane cholesterol decrease, followed by a second calcium-dependent increase. Third, lipid domains mainly enriched in GM1 or sphingomyelin strongly increased from the 1st week while those mainly enriched in cholesterol or ceramide decreased during the 1st and 4th week, respectively. Fourth, the plasmatic acid sphingomyelinase activity considerably increased upon storage following the sphingomyelin-enriched domain rise and potentially inducing the loss of ceramide-enriched domains. Fifth, in support of the shedding of cholesterol- and ceramide-enriched domains from the RBC surface, the number of cholesterol-enriched domains lost and the abundance of EVs released during the 1st week perfectly matched. Moreover, RBC-derived EVs were enriched in ceramide at the 4th week but depleted in sphingomyelin. Then, using K/EDTA tubes supplemented with glucose to longer preserve the ATP content, we better defined the sequence of events. Altogether, we showed that EV shedding from lipid domains only represents part of the global vesiculation mechanistics, for which we propose four successive events (cholesterol domain decrease, oxidative stress, sphingomyelin/sphingomyelinase/ceramide/calcium alteration and phosphatidylserine exposure).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350142PMC
July 2020

Growth performance and immune status in common carp Cyprinus carpio as affected by plant oil-based diets complemented with β-glucan.

Fish Shellfish Immunol 2019 Sep 11;92:288-299. Epub 2019 Jun 11.

Research Unit in Environmental and Evolutionary Biology (URBE), Institute of Life, Earth and Environment (ILEE), University of Namur, Belgium. Electronic address:

Omnivorous fish species such as the common carp (Cyprinus carpio) are able to biosynthesise long chain polyunsaturated fatty acids (LC-PUFAs) from plant oil PUFA precursors, but the influence of the amount and quality of the LC-PUFAs biosynthesised from these oils on the immunocompetence status of the fish has received little attention. This study aims to evaluate whether the conversion of PUFA by carp induces a sufficient biosynthesis of LC-PUFA to maintain a good immunocompetence status in this species. Six iso-nitrogenous (crude protein = 39.1%) and iso-lipidic (crude lipids = 10%) diets containing three different lipid sources (cod liver oil (CLO) as fish oil; linseed oil (LO) and sunflower oil (SFO) as plant oils) were formulated with or without β-glucan supplementation at 0.25 g/kg diet. Juvenile carp (16.3 ± 0.6 g initial body weight) were fed a daily ration of 4% body weight for 9 weeks and then infected at day 64 with the bacteria Aeromonas hydrophyla. No significant differences in survival rate, final body weight, specific growth rate and feed conversion rate were observed between diets. After bacterial infection, mortality rate did not differ between fish fed CLO and plant oil-based diets, indicating that the latter oils did not affect the overall immunocompetence status of common carp. Plant oil-based diets did not alter lysozyme activity in healthy and infected fish. No negative effects of plant oils on complement activity (ACH50) were observed in healthy fish, even if both plant oil-based diets induced a decrease in stimulated fish two days after infection. Furthermore, the levels of various immune genes (nk, lys, il-8, pla, pge, alox) were not affected by plant oil-based diets. The expression of pla and pge genes were higher in SFO-fed fish than in CLO ones, indicating that this plant oil rich in linoleic acid (LA) better stimulated the eicosanoid metabolism process than fish oil. In response to β-glucan supplementation, some innate immune functions seemed differentially affected by plant oil-based diets. LO and SFO induced substantial LC-PUFA production, even if fish fed CLO displayed the highest EPA and DHA levels in tissues. SFO rich in LA induced the highest ARA levels in fish muscle while LO rich in α-linolenic acid (ALA) sustained higher EPA production than SFO. A significantly higher fads-6a expression level was observed in SFO fish than in LO ones, but this was not observed for elovl5 expression. In conclusion, the results show that common carp fed plant oil-based diets are able to produce substantial amounts of LC-PUFA for sustaining growth rate, immune status and disease resistance similar to fish fed a fish oil-based diet. The differences in the production capacity of LC-PUFAs by the two plant oil-based diets were associated to a differential activation of some immune pathways, explaining how the use of these oils did not affect the overall immunocompetence of fish challenged with bacterial infection. Moreover, plant oil-based diets did not induce substantial negative effects on the immunomodulatory action of β-glucans, confirming that these oils are suitable for sustaining a good immunocompetence status in common carp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2019.06.011DOI Listing
September 2019

High hydrostatic pressure influences the in vitro response to xenobiotics in Dicentrarchus labrax liver.

Aquat Toxicol 2016 Apr 13;173:43-52. Epub 2016 Jan 13.

Institut des Sciences de la Vie, Université Catholique de Louvain, Croix du Sud 2, B-1348 Louvain-la-Neuve, Belgium. Electronic address:

Hydrostatic pressure (HP) increases by about 1 atmosphere (0.1MPa) for each ten-meter depth increase in the water column. This thermodynamical parameter could well influence the response to and effects of xenobiotics in the deep-sea biota, but this possibility remains largely overlooked. To grasp the extent of HP adaptation in deep-sea fish, comparative studies with living cells of surface species exposed to chemicals at high HP are required. We initially conducted experiments with precision-cut liver slices of a deep-sea fish (Coryphaenoides rupestris), co-exposed for 15h to the aryl hydrocarbon receptor (AhR) agonist 3-methylcholanthrene at HP levels representative of the surface (0.1MPa) and deep-sea (5-15MPa; i.e., 500-1500m depth) environments. The transcript levels of a suite of stress-responsive genes, such as the AhR battery CYP1A, were subsequently measured (Lemaire et al., 2012; Environ. Sci. Technol. 46, 10310-10316). Strikingly, the AhR agonist-mediated increase of CYP1A mRNA content was pressure-dependently reduced in C. rupestris. Here, the same co-exposure scenario was applied for 6 or 15h to liver slices of a surface fish, Dicentrarchus labrax, a coastal species presumably not adapted to high HP. Precision-cut liver slices of D. labrax were also used in 1h co-exposure studies with the pro-oxidant tert-butylhydroperoxide (tBHP) as to investigate the pressure-dependence of the oxidative stress response (i.e., reactive oxygen production, glutathione and lipid peroxidation status). Liver cells remained viable in all experiments (adenosine triphosphate content). High HP precluded the AhR agonist-mediated increase of CYP1A mRNA expression in D. labrax, as well as that of glutathione peroxidase, and significantly reduced that of heat shock protein 70. High HP (1h) also tended per se to increase the level of oxidative stress in liver cells of the surface fish. Trends to an increased resistance to tBHP were also noted. Whether the latter observation truly reflects a protective response to oxidative stress will be addressed in future co-exposure studies with both surface and deep-sea fish liver cells, using additional pro-oxidant chemicals. Altogether, data on CYP1A inducibility with D. labrax and C. rupestris support the view that high HP represses AhR signaling in marine fishes, and that only species adapted to thrive in the deep-sea have evolved the molecular adaptations necessary to counteract to some extent this inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aquatox.2016.01.004DOI Listing
April 2016

PCB-153 shows different dynamics of mobilisation from differentiated rat adipocytes during lipolysis in comparison with PCB-28 and PCB-118.

PLoS One 2014 11;9(9):e106495. Epub 2014 Sep 11.

Institut des Sciences de la Vie, Université catholique de Louvain, Louvain-la-Neuve, Belgium.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants. Due to their lipophilic character, they are preferentially stored within the adipose tissue. During the mobilisation of lipids, PCBs might be released from adipocytes into the bloodstream. However, the mechanisms associated with the release of PCBs have been poorly studied. Several in vivo studies followed their dynamics of release but the complexity of the in vivo situation, which is characterised by a large range of pollutants, does not allow understanding precisely the behaviour of individual congeners. The present in vitro experiment studied the impact of (i) the number and position of chlorine atoms of PCBs on their release from adipocytes and (ii) the presence of other PCB congeners on the mobilisation rate of such molecules.

Methodology/principal Findings: Differentiated rat adipocytes were used to compare the behaviour of PCB-28, -118 and -153. Cells were contaminated with the three congeners, alone or in cocktail, and a lipolysis was then induced with isoproterenol during 12 hours. Our data indicate that the three congeners were efficiently released from adipocytes and accumulated in the medium during the lipolysis. Interestingly, for a same level of cell lipids, PCB-153, a hexa-CB with two chlorine atoms in ortho-position, was mobilised slower than PCB-28, a tri-CB, and PCB-118, a penta-CB, which are both characterised by one chlorine atom in ortho-position. It suggests an impact of the chemical properties of pollutants on their mobilisation during periods of negative energy balance. Moreover, the mobilisation of PCB congeners, taken individually, did not seem to be influenced by the presence of other congeners within adipocytes.

Conclusion/significance: These results not only highlight the obvious mobilisation of PCBs from adipocytes during lipolysis, in parallel to lipids, but also demonstrate that the structure of congeners defines their rate of release from adipocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106495PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161324PMC
May 2015

Nutritional composition and antioxidant properties of the sim fruit (Rhodomyrtus tomentosa).

Food Chem 2015 Feb 23;168:410-6. Epub 2014 Jul 23.

Institut des Sciences de la Vie, UCLouvain, Belgium.

In this study, detailed chemical properties of sim (Rhodomyrtus tomentosa (Ait.) Hassk.) fruit including nutritional composition, phenolic content and antioxidant capacity were determined for the first time. A 150g serving of sim fruit contained high levels of dietary fibre (69.94-87.43% of Recommended Daily Intake (RDI)), α-tocopherol (38.90-51.87% RDI), manganese (>100% RDI), and copper (44.44% RDI) but low levels of protein (2.63% RDI), lipid (1.59-3.5% RDI), and sugars (5.65% RDI). The predominant fatty acid in the sim fruit sample was linoleic acid (75.36% of total fatty acids). Interestingly, total phenolics (49.21±0.35mg gallic acid equivalent (GAE)/g dry weight (DW)) were particularly high and resulted in a high antioxidant capacity (431.17±14.56μmol Trolox equivalent (TE)/g DW). These results, together with our recent discovery of high amount of piceatannol, a stilbene with potent biological activities, highlight the potential of sim, an under-utilised plant species from South-East Asia, as a new source of health-promoting compounds including dietary fibres, essential fatty acids, and phenolic compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2014.07.081DOI Listing
February 2015

Fatty acid mobilization and comparison to milk fatty acid content in northern elephant seals.

J Comp Physiol B 2014 Jan 15;184(1):125-35. Epub 2013 Oct 15.

Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, USA,

A fundamental feature of the life history of true seals, bears and baleen whales is lactation while fasting. This study examined the mobilization of fatty acids from blubber and their subsequent partitioning into maternal metabolism and milk production in northern elephant seals (Mirounga angustirostris). The fatty acid composition of blubber and milk was measured in both early and late lactation. Proportions of fatty acids in milk and blubber were found to display a high degree of similarity both early and late in lactation. Seals mobilized an enormous amount of lipid (~66 kg in 17 days), but thermoregulatory fatty acids, those that remain fluid at low temperatures, were relatively conserved in the outer blubber layer. Despite the stratification, the pattern of mobilization of specific fatty acids conforms to biochemical predictions. Long chain (>20C) monounsaturated fatty acids (MUFAs) were the least mobilized from blubber and the only class of fatty acids that showed a proportional increase in milk in late lactation. Polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs) were more mobilized from the blubber, but neither proportion increased in milk at late lactation. These data suggest that of the long chain MUFA mobilized, the majority is directed to milk synthesis. The mother may preferentially use PUFA and SFA for her own metabolism, decreasing the availability for deposition into milk. The potential impacts of milk fatty acid delivery on pup diving development and thermoregulation are exciting avenues for exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00360-013-0787-7DOI Listing
January 2014

Polyunsaturated fatty acid metabolism in enterocyte models: T84 cell line vs. Caco-2 cell line.

In Vitro Cell Dev Biol Anim 2014 Feb 27;50(2):111-20. Epub 2013 Aug 27.

Institut des Sciences de la Vie & UCLouvain, Louvain-la-Neuve, Belgium.

Human colon carcinoma cell lines such as Caco-2 cells, model of mature enterocytes and T84 cells, model of crypt cells are useful to study interactions between nutrient processing and metabolic functions at intestinal level. Our study aimed at comparing the ability of Caco-2 and T84 cells (1) to incorporate dietary polyunsaturated fatty acids (PUFA), (2) to process them and (3) to sort them into neutral lipids (NL), free fatty acids (FFA) and phospholipids (PL). Caco-2 and T84 cells were exposed to a 7-day long supplementation with PUFA. The amounts of fatty acids accumulated and incorporated into the NL, FFA or PL fractions were higher in Caco-2 than in T84 cells. Caco-2 cells were able to significantly elongate C18 PUFA and C20 PUFA of both n-3 and n-6 families. In contrast, T84 cells were unable to elongate the n-6 fatty acids whereas elongation of n-3 fatty acids was detectable but marginal. Similarly, a Δ6 desaturase activity was observed in Caco-2 but not in T84 cells. In T84 cells, each exogenous fatty acid was predominantly accumulated in the PL fraction. In Caco-2 cells, C20 fatty acids and C18:2n-6 was preferentially accumulated in the PL fraction, while C22 PUFA and C18:3n-3 was preferentially accumulated in the NL fraction. Overall, this study has shown that Caco-2 and T84 cells, as models of intestinal mucosal cells, present large differences in PUFA accumulation capacity, specific elongase and desaturase activities and distribution pattern of exogenous PUFA and of their metabolites in the lipid classes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11626-013-9682-5DOI Listing
February 2014

Sacha inchi (Plukenetia volubilis): a seed source of polyunsaturated fatty acids, tocopherols, phytosterols, phenolic compounds and antioxidant capacity.

Food Chem 2013 Dec 3;141(3):1732-9. Epub 2013 May 3.

Instituto de Biotecnología (IBT), Universidad Nacional Agraria La Molina-UNALM, Av., La Molina s/n, Lima, Peru.

Fatty acids (FA), phytosterols, tocopherols, phenolic compounds, total carotenoids and hydrophilic and lipophilic ORAC antioxidant capacities were evaluated in 16 cultivars of Sacha inchi (SI) seeds with the aim to valorise them and offer more information on the functional properties of SI seeds. A high α linolenic (α-Ln) fatty acid content was found in all cultivars (ω3, 12.8-16.0 g/100 g seed), followed by linoleic (L) fatty acid (ω6, 12.4-14.1g/100g seed). The ratio ω6/ω3 was within the 0.83-1.09 range. γ- and δ-tocopherols were the most important tocopherols, whereas the most representative phytosterols were β-sitosterol and stigmasterol. Contents of total phenolics, total carotenoids and hydrophilic and lipophilic antioxidant capacities ranged from 64.6 to 80 mg of gallic acid equivalent/100g seed; from 0.07 to 0.09 mg of β-carotene equivalent/100g of seed; from 4.3 to 7.3 and, from 1.0 to 2.8 μmol of Trolox equivalent/g of seed, respectively, among the evaluated SI cultivars. Results showed significant differences (p<0.05) among the evaluated SI cultivars in the contents of ω3, ω6, antioxidant capacities and other evaluated phytochemicals. SI seeds should be considered as an important dietary source of health promoting phytochemicals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2013.04.078DOI Listing
December 2013

Differential changes of fat-soluble vitamins and pollutants during lactation in northern elephant seal mother-pup pairs.

Comp Biochem Physiol A Mol Integr Physiol 2012 Aug 6;162(4):323-30. Epub 2012 Apr 6.

Institut des Sciences de la Vie, Université catholique de Louvain, Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve, Belgium.

We investigated the changes of vitamins A and E as well as PCBs and DDTs during lactation in northern elephant seal (Mirounga angustirostris) mother-pup pairs. On average, milk vitamin A concentrations were 6 times higher during late lactation than during early lactation, a pattern that differs dramatically from terrestrial mammals. Vitamin A concentrations also significantly increased in the inner blubber throughout lactation, whereas they remained constant in the outer blubber. Similar dynamics were observed for PCBs and DDTs in maternal blubber and milk. Blubber appears to be an important storage site for vitamin A and organochlorines in seals and a direct transfer of those molecules to the mammary gland may occur. The dynamics of vitamin A, PCBs and DDTs differed from those of vitamin E. There was a significant drop in milk vitamin E concentrations between early and late lactation, which is the usual pattern observed in terrestrial mammals. The dynamics of vitamin E in the blubber layers also differed from those of vitamin A, suggesting different mechanisms of mobilization and transfer into the milk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbpa.2012.04.001DOI Listing
August 2012

Uptake of conjugated linolenic acids and conversion to cis-9, trans-11-or trans-9, trans-11-conjugated linoleic acids in Caco-2 cells.

Br J Nutr 2013 Jan 4;109(1):57-64. Epub 2012 Apr 4.

Institut des Sciences de la Vie, Université catholique de Louvain, Croix du Sud, 2, bte L7·05·08, B-1348 Louvain-La-Neuve, Belgium.

Dietary oils containing large amounts of conjugated linolenic acids (CLnA) may be regarded as a source of conjugated linoleic acids (CLA), which have been suspected to bear health-promoting properties. Indeed, CLnA can be converted into CLA in mammals. The objective of the present study was to investigate the uptake of CLnA and their metabolism into CLA in Caco-2 cells, as a validated in vitro model of the intestinal barrier. Caco-2 cells were incubated for 24 h in the presence of either α-eleostearic, β-eleostearic, catalpic or punicic acid. We first observed that Caco-2 cells take these CLnA up at different rates and then convert them but with varying efficiency depending on the structure of the Δ13 double bond. Finally, the distribution of CLnA between neutral lipids (NL) and phospholipids appeared to be linked to their number of trans double bonds: the higher the number, the higher the accumulation in the NL fraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114512000608DOI Listing
January 2013

Conversion of t11t13 CLA into c9t11 CLA in Caco-2 cells and inhibition by sterculic oil.

PLoS One 2012 12;7(3):e32824. Epub 2012 Mar 12.

Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Background: Conjugated linoleic acids (CLA), and principally c9t11 CLA, are suspected to have numerous preventive properties regarding non-infectious pathologies such as inflammatory diseases, atherosclerosis and several types of cancer. C9t11 CLA is produced in the rumen during biohydrogenation of linoleic acid, but can also be synthesized in mammalian tissues from trans-vaccenic acid (C18:1 t11) through the action of delta-9 desaturase (D9D). For several years, it is also known that c9t11 CLA can be synthesized from conjugated linolenic acids (CLnA), i.e. c9t11c13 CLnA and c9t11t13 CLnA. This study aimed at investigating to which extent and by which route c9t11 CLA can be produced from another isomer of CLA, the t11t13 CLA that is structurally very similar to c9t11t13 CLnA, in Caco-2 cells.

Methodology/principal Findings: Caco-2 cells were incubated for 24 h with 20 µmol/l of t11t13 CLA in the absence or presence of sterculic oil used as an inhibitor of D9D. Caco-2 cells were able to convert t11t13 CLA into c9t11 CLA, and c9t11t13 CLnA was formed as an intermediate compound. In the presence of sterculic oil, the production of this intermediate was decreased by 46% and the formation of c9t11 CLA was decreased by 26%. No other metabolite was detected.

Conclusions/significance: These results not only highlight the conversion of t11t13 CLA into c9t11 CLA but demonstrate also that this conversion involves first a desaturation step catalysed by D9D to produce c9t11t13 CLnA and then the action of another enzyme reducing the double bond on the Δ13 position.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032824PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299700PMC
August 2012

Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARγ-related adipogenesis in the white adipose tissue of high-fat diet-fed mice.

J Nutr Biochem 2011 Aug 5;22(8):712-22. Epub 2010 Nov 5.

Louvain Drug Research Institute, Metabolism and Nutrition Research Group, LDRI, Université Catholique de Louvain, 1200 Brussels, Belgium.

Inulin-type fructans (ITF) are nondigestible/fermentable carbohydrates which are able - through the modification of the gut microbiota - to counteract high-fat (HF) diet-induced obesity, endotoxemia and related-metabolic alterations. However, their influence on adipose tissue metabolism has been poorly studied until now. The aim of this study was to assess the influence of ITF supplementation on adipose tissue metabolism, by focusing on a G protein-coupled receptor (GPR), GPR43, as a potential link between gut fermentation processes and white adipose tissue development. Male C57bl6/J mice were fed a standard diet or an HF diet without or with ITF (0.2 g/day per mouse) during 4 weeks. The HF diet induced an accumulation of large adipocytes, promoted peroxisome proliferator activated receptor gamma (PPARγ)-activated differentiation factors and led to a huge increase in GPR43 expression in the subcutaneous adipose tissue. All those effects were blunted by ITF treatment, which modulated the gut microbiota in favor of bifidobacteria at the expense of Roseburia spp. and of Clostridium cluster XIVa. The dietary modulation of GPR43 expression seems independent of endotoxemia, in view of data obtained in vivo (acute and chronic lipopolysaccharides treatment). In conclusion, ITF, which promote gut fermentation, paradoxically counteract GPR43 overexpression induced in the adipose tissue by an HF diet, a phenomenon that correlates with a beneficial effect on adiposity and with potential decrease in PPARγ-activated processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jnutbio.2010.05.009DOI Listing
August 2011

Determination by fourier transform Raman spectroscopy of conjugated linoleic acid in I2-photoisomerized soybean oil.

J Agric Food Chem 2009 Aug;57(15):6524-7

Unite de Biochimie de la Nutrition, Faculte d'Ingenierie Biologique, Agronomique et Environnementale, Universite Catholique de Louvain (UCL), Croix du Sud 2 (bte 8), 1348 Louvain la Neuve, Belgium.

The potential of Fourier transform (FT)-Raman spectroscopy to quantify the total conjugated linoleic acid (CLA) content was evaluated to find a technique for the routine control of CLA synthesis by chemical procedures. The calibration and validation samples were obtained by photoisomerization of linoleic acid contained in soybean oil. The catalyst was iodine (I(2)), and the light source was the green line (514.5 nm) of an argon ion laser. The criteria to select the best partial least-squares (PLS) calibration model were a low standard error of prediction (SEP), a high correlation coefficient (R), and the selection of relevant variables of the Raman spectrum to reduce spectral interferences. The total CLA content of the 22 samples ranged from 0.05 to 3.28% of total lipids. The best PLS calibration model was obtained with three optimal factors, a SEP of 0.22, and a R of 0.97. This calibration model was obtained after baseline correction of the CC stretching region (1642-1680 cm(-1)), which contained sufficient spectral information for reliable CLA quantification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jf9003237DOI Listing
August 2009

Performance comparison of UV and FT-Raman spectroscopy in the determination of conjugated linoleic acids in cow milk fat.

J Agric Food Chem 2008 Feb 5;56(4):1159-63. Epub 2008 Feb 5.

Unité de biochimie de la nutrition, Faculté d'ingénierie biologique, agronomique et environnementale, Université catholique de Louvain, Louvain la neuve, Belgium.

The determination of conjugated linoleic acids (CLA) in cow milk fat was studied by using UV (210-250 nm) and Fourier transform (FT)-Raman (900-3400 cm (-1)) spectroscopy in order to determine the best spectrophotometric technique for routine analysis of milk fat. A collection of 57 milk fat samples was randomly divided into two sets, a calibration set and a validation set, representing two-thirds and one-third of the samples, respectively. All calculations were performed on the calibration set and then applied to the validation set. The CLA content ranged from 0.56 to 4.70%. A comparison of various spectral pretreatments and different multivariate calibration techniques, such as partial least-squares (PLS) and multiple linear regression (MLR), was done. This paper shows that UV spectroscopy is as reliable as FT-Raman spectroscopy to monitor CLA in cow milk fat. The best calibration for FT-Raman was given by a PLS model of seven factors with a standard error of prediction (SEP) of 0.246. For UV spectroscopy, PLS models were also better than MLR models. The most robust PLS model was constructed with only one factor and with SEP=0.288.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jf703712wDOI Listing
February 2008

Determination of the conjugated linoleic acids in cow's milk fat by Fourier transform Raman spectroscopy.

J Agric Food Chem 2005 Jul;53(15):5831-5

Unité de Biochimie de la Nutrition, Faculté d'Ingénierie biologique, agronomique et environnementale, Université catholique de Louvain, Croix du Sud 2, 1348 Louvain-la-Neuve, Belgium.

The collective term "conjugated linoleic acid" or "CLA" generally refers to a mixture of conjugated positional and geometric isomers of linoleic (cis-9,cis-12-octodecadienoic) acid. In nature, these isomers are mainly formed in the rumen by biohydrogenation of polyunsaturated fatty acids. This study concerns a first trial of CLA determination in cow's milk fat by Raman spectroscopy. The spectra of pure cis-9-oleic, cis-9,cis-12-linoleic, cis-9,trans-11-linoleic, and trans-10,cis-12-linoleic acids have been examined in comparison with the spectra of selected milk-fat samples containing between 0 and 3% of CLA. The trial of CLA determination by Raman spectroscopy on cow milk fat has reached its objective with the two following results. First, the examination of the Raman spectra allows to identify three specific Raman signals of the chemical bonds associated to the cis,trans conjugated C=C in the rumenic and trans-10,cis-12-octodecadienoic acids at 1652, 1438, and 3006 cm(-1). Second, the calibration of Raman spectrometer for the CLA determination has indicated that these three specific signals suit very well for the accurate and reliable measurement of CLA concentration in milk fat. To our knowledge, the present study is the first successful attempt to determine the CLA content of milk fat by a spectrophotometric method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jf0480795DOI Listing
July 2005

Spelt (Triticum aestivum ssp. spelta) as a source of breadmaking flours and bran naturally enriched in oleic acid and minerals but not phytic acid.

J Agric Food Chem 2005 Apr;53(7):2751-9

Unité de biochimie de la nutrition, Université catholique de Louvain, Croix du Sud 2/8, 1348 Louvain-la-Neuve, Belgium.

The nutritional value of breadmaking cereal spelt (Triticum aestivum ssp. spelta) is said to be higher than that of common wheat (Triticum aestivum ssp. vulgare), but this traditional view is not substantiated by scientific evidence. In an attempt to clarify this issue, wholemeal and milling fractions (sieved flour, fine bran, and coarse bran) from nine dehulled spelt and five soft winter wheat samples were compared with regard to their lipid, fatty acid, and mineral contents. In addition, tocopherol (a biochemical marker of germ) was measured in all wholemeals, whereas phytic acid and phosphorus levels were determined in fine bran and coarse bran samples after 1 month of storage. Results showed that, on average, spelt wholemeals and milling fractions were higher in lipids and unsaturated fatty acids as compared to wheat, whereas tocopherol content was lower in spelt, suggesting that the higher lipid content of spelt may not be related to a higher germ proportion. Although milling fractionation produced similar proportions of flour and brans in spelt and wheat, it was found that ash, copper, iron, zinc, magnesium, and phosphorus contents were higher in spelt samples, especially in aleurone-rich fine bran and in coarse bran. Even though phosphorus content was higher in spelt than in wheat brans, phytic acid content showed the opposite trend and was 40% lower in spelt versus wheat fine bran, which may suggest that spelt has either a higher endogenous phytase activity or a lower phytic acid content than wheat. The results of this study give important indications on the real nutritional value of spelt compared to wheat. Moreover, they show that the Ca/Fe ratio, combined with that of oleate/palmitate, provides a highly discriminating tool to authenticate spelt from wheat flours and to face the growing issue of spelt flour adulteration. Finally, they suggest that aleurone differences, the nature of which still needs to be investigated, may account for the differential nutrient composition of spelt and wheat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jf048506eDOI Listing
April 2005
-->