Publications by authors named "Yvan Larondelle"

98 Publications

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

Impact of Protein-Enriched Plant Food Items on the Bioaccessibility and Cellular Uptake of Carotenoids.

Antioxidants (Basel) 2021 Jun 23;10(7). Epub 2021 Jun 23.

Department of Population Health, Luxembourg Institute of Health, 1445 Strassen, Luxembourg.

Carotenoids are lipophilic pigments which have been associated with a number of health benefits, partly related to antioxidant effects. However, due to their poor solubility during digestion, carotenoid bioavailability is low and variable. In this study, we investigated the effect of frequently consumed proteins on carotenoid bioaccessibility and cellular uptake. Whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (SC), gelatin (GEL), turkey and cod, equivalent to 0/10/25/50% of the recommended dietary allowance (RDA, approx. 60g/d), were co-digested gastro-intestinally with carotenoid-rich food matrices (tomato and carrot juice, spinach), and digesta further studied in Caco-2 cell models. Lipid digestion, surface tension and microscopic visualization were also carried out. Co-digested proteins positively influenced the micellization of carotenes (up to 3-fold, depending on type and concentration), especially in the presence of SPI ( < 0.001). An increased cellular uptake was observed for xanthophylls/carotenes (up to 12/33%, < 0.001), which was stronger for matrices with an initially poor carotenoid micellization (i.e., tomato juice, < 0.001), similar to what was encountered for bioaccessibility. Turkey and cod had a weaker impact. Significant interactions between carotenoids, lipids and proteins were observed during digestion. Co-digested proteins generally improved lipid digestion in all matrices ( < 0.001), especially for carrot juice, though slight decreases were observed for GEL. Protein impact on the surface tension was limited. In conclusion, proteins generally improved both carotenoid bioaccessibility and cellular uptake, depending on the matrices and carotenoid-type (i.e., carotene vs. xanthophylls), which may be relevant under specific circumstances, such as intake of carotenoid-rich food items low in lipids.
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http://dx.doi.org/10.3390/antiox10071005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300660PMC
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.
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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.
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http://dx.doi.org/10.3390/foods10051134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160806PMC
May 2021

Modulations of lipid metabolism and development of the Atlantic salmon (Salmo salar) fry in response to egg-to-fry rearing conditions.

Fish Physiol Biochem 2021 Aug 11;47(4):979-997. Epub 2021 May 11.

Research Unit in Environmental and Evolutionary Biology (URBE), Institute of Life, Earth & Environment, University of Namur (UNamur), 5000, Namur, Belgium.

In stocking program, the use of artificial incubation conditions in hatcheries from the fertilisation of eggs to the release of unfed fry could reduce their ability to adapt to the natural environment. This study evaluates the effects of three factors on the fitness and physiology of salmon fry at their emergence, the origin of water (river vs drilling), the type of support in the incubator (support matrix vs plastic sheets) and the type of incubators (Californian vs vertical trays), and compares them to a semi-natural incubation method in river. Key biological functions including nutritional and immune status were compared among experimental conditions using biometric parameters, lipid composition and gene expression analyses. Our findings demonstrated that fry incubated in vertical trays supplied with river water had no significant difference in growth and lipid composition compared to those in semi-natural incubators. Besides, fry incubated on a substrate matrix in Californian trays exhibited phenotypic characteristics closest to those incubated in river. This support matrix improved fish growth, lipid consumption and distribution compared to fry on plastic sheets. Moreover, the large amounts of several PUFAs in these fry could allow a better membrane fluidity ensuring a better adaptation to temperature variation under cold conditions. In addition, drilling water improved the survival rate compared to river water due to lower numbers of fine particles, known to be responsible for the clogging of eggs. To conclude, using a substrate combined with drilling water in artificial incubators could increase fry fitness and its adaption to wild life.
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http://dx.doi.org/10.1007/s10695-021-00959-0DOI Listing
August 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.
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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.
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http://dx.doi.org/10.3390/nu13020663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923083PMC
February 2021

Lipolysis and Leptin Production of Elephant Seal Blubber Using Precision-Cut Adipose Tissue Slices.

Front Physiol 2020 10;11:615784. Epub 2020 Dec 10.

Department of Biology, Sonoma State University, Rohnert Park, CA, United States.

Adipose tissue plays key roles in energy homeostasis. Understanding its metabolism and regulation is essential to predict the impact of environmental changes on wildlife health, especially in fasting-adapted species. However, experimental work in wild vertebrates can be challenging. We have developed a novel approach of precision-cut adipose tissue slices from northern elephant seal () as a complementary approach to whole animal models. Blubber biopsies were collected from 14 pups during early and late post-weaning fast (Año Nuevo, CA, United States), precision-cut into 1 mm thick slices and maintained in culture at 37°C for at least 63 h. The slices exhibited an efficient response to ß-adrenergic stimulation, even after 2 days of culture, revealing good tissue function. The response to lipolytic stimulus did not vary between regions of outer and inner blubber, but was higher at early than at late fast for inner blubber slices. At early fast, lipolysis significantly reduced leptin production. At this stage, inner blubber slices were also more efficient at producing leptin than outer blubber slices, especially in the non-lipolytic condition. This model will aid the study of adipose tissue metabolism and its response to environmental stressors in marine mammals.
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http://dx.doi.org/10.3389/fphys.2020.615784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758477PMC
December 2020

Interplay between dietary lipids and cadmium exposure in rainbow trout liver: Influence on fatty acid metabolism, metal accumulation and stress response.

Aquat Toxicol 2021 Feb 30;231:105676. Epub 2020 Nov 30.

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

The present study aimed at investigating interactive effects between dietary lipids and both short- and long-term exposures to a low, environmentally realistic, cadmium (Cd) concentration. Juvenile rainbow trout were fed four isolipidic diets (31.7 g/kg) enriched in either linoleic acid (LA, 18:2n-6), alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3) or docosahexaenoic acid (DHA, 22:6n-3). From the 4th week of this 10-week experiment, the lipid level of the diet was increased (120.0 g/kg) and half of the fish fed each diet were aqueously exposed to Cd (0.3 μg/L) while the other half were not exposed to Cd (control). Fish were sampled and their liver was harvested for fatty acid profile, hepatic Cd and calcium concentrations, total glutathione level and gene expression assessment, either (i) after 4 weeks of feeding and 24 h of Cd contamination (day 29) (short-term Cd exposure) or (ii) after 10 weeks of feeding and 6 weeks of Cd contamination (day 70) (long-term Cd exposure). We found that both dietary lipids and Cd exposure influenced fatty acid homeostasis and metabolism. The hepatic fatty acid profile mostly reflected that of the diet (e.g. n-3/n-6 ratio) with some differences, including selective retention of specific long chain polyunsaturated fatty acids (LC-PUFAs) like DHA and active biotransformation of dietary LA and ALA into LC-PUFAs. Cd effects on hepatic fatty acid profiles were influenced by the duration of the exposure and the nutritional status of the fish. The effects of diet and Cd exposure on the fatty acid profiles were only sparsely explained by variation of the expression pattern of genes involved in fatty acid metabolism. The biological responses to Cd were also influenced by dietary lipids. Fish fed the ALA-enriched diet seemed to be the least affected by the Cd exposure, as they showed a higher detoxifying ability against Cd with an early upregulation of protective metallothionein a (MTa) and apoptosis regulator BCL2-Like1 (BCLx) genes, an increased long-term phospholipid synthesis and turnover and fatty acid bioconversion efficiency, as well as a lower long-term accumulation of Cd in their liver. In contrast, fish fed the EPA-enriched diet seemed to be the most sensitive to a long-term Cd exposure, with an impaired growth performance and a decreased antioxidant capacity (lower glutathione level). Our results highlight that low, environmentally realistic aqueous concentrations of Cd can affect biological response in fish and that these effects are influenced by the dietary fatty acid composition.
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http://dx.doi.org/10.1016/j.aquatox.2020.105676DOI Listing
February 2021

Methylmercury displays pro-adipogenic properties in rainbow trout preadipocytes.

Chemosphere 2021 Jan 17;263:127917. Epub 2020 Aug 17.

Louvain Institute of Biomolecular Science and Technology (LIBST), Université catholique de Louvain, Croix Du Sud 4-5/L7.07.03, 1348, Louvain-la-Neuve, Belgium. Electronic address:

Methylmercury (MeHg) is a ubiquitous contaminant largely found in aquatic environments, especially in species at high trophic level such as salmonids. The aim of this study was to evaluate the effects of MeHg on adipocyte differentiation and lipid metabolism in rainbow trout. Primary cultured preadipocytes were exposed to increasing concentrations of MeHg during six days with or without a hormonal cocktail. Main results showed a dose-dependent intracellular accumulation of neutral lipids with a preferential uptake of n-3 polyunsaturated fatty acids. Interestingly, this accumulation occurred after a fairly low uptake of MeHg by preadipocytes and was maintained after the cellular exposure to MeHg. In membrane phospholipids, arachidonic acid (20:4 n-6) was released in a dose-dependent manner. At the transcriptional level, the expression of several adipocyte-specific genes (perilipin 2 and apolipoprotein Eb) as well as lipid-related genes (fatty acid synthase and fatty acid binding protein 11a) was up-regulated in preadipocytes exposed to MeHg. These results highlight for the first time the disrupting effect of MeHg in trout adipocyte metabolism, providing new insights regarding the role of environmental pollutants in adipose tissue dysfunction and related pathologies.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127917DOI Listing
January 2021

Cancer diets for cancer patients: Lessons from mouse studies and new insights from the study of fatty acid metabolism in tumors.

Biochimie 2020 Nov 3;178:56-68. Epub 2020 Sep 3.

Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, 57 Avenue Hippocrate B1.57.04, B-1200, Brussels, Belgium. Electronic address:

Specific diets for cancer patients have the potential to offer an adjuvant modality to conventional anticancer therapy. If the concept of starving cancer cells from nutrients to inhibit tumor growth is quite simple, the translation into the clinics is not straightforward. Several diets have been described including the Calorie-restricted diet based on a reduction in carbohydrate intake and the Ketogenic diet wherein the low carbohydrate content is compensated by a high fat intake. As for other diets that deviate from normal composition only by one or two amino acids, these diets most often revealed a reduction in tumor growth in mice, in particular when associated with chemo- or radiotherapy. By contrast, in cancer patients, the interest of these diets is almost exclusively supported by case reports precluding any conclusions on their real capacity to influence disease outcome. In parallel, the field of tumor lipid metabolism has emerged in the last decade offering a better understanding of how fatty acids are captured, synthesized or stored as lipid droplets in cancers. Fatty acids participate to cancer cell survival in the hypoxic and acidic tumor microenvironment and also support proliferation and invasiveness. Interestingly, while such addiction for fatty acids may account for cancer progression associated with high fat diet, it could also represent an Achilles heel for tumors. In particular n-3 polyunsaturated fatty acids represent a class of lipids that can exert potent cytotoxic effects in tumors and therefore represent an attractive diet supplementation to improve cancer patient outcomes.
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http://dx.doi.org/10.1016/j.biochi.2020.08.020DOI Listing
November 2020

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

Influence of soy and whey protein, gelatin and sodium caseinate on carotenoid bioaccessibility.

Food Funct 2020 Jun;11(6):5446-5459

Luxembourg Institute of Health, Department of Population Health, Nutrition and Health Research Group, Strassen, Luxembourg.

Proteins could alter carotenoid bioaccessibility through altering their fate during digestion, due to emulsifying properties of resulting peptides, or influencing access of digestion enzymes to lipid droplets. In this investigation, we studied whether whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (SC) and gelatin (GEL), added at various concentrations (expressed as percentage of recommended dietary allowance (RDA): 0, 10, 25 and 50%) would influence the bioaccessibility of lycopene, β-carotene or lutein, added as pure carotenoids solubilized in oil, during simulated gastro-intestinal (GI) digestion. Protein and lipid digestion as well as selected physico-chemical parameters including surface tension, ζ-potential and micelle size were evaluated. Adding proteins influenced positively the bioaccessibility of β-carotene, by up to 189% (p < 0.001), but it resulted in generally decreased bioaccessibility of lutein, by up to 50% (p < 0.001), while for lycopene, the presence of proteins did not influence its bioaccessibility, except for a slight increase with WPI, by up to 135% (p < 0.001). However, the effect depended significantly on the type of protein (p < 0.001) and its concentration (p < 0.001). While β-carotene bioaccessibility was greatly enhanced in the presence of SC, compared to WPI and GEL, the presence of SPI strongly decreased carotenoid bioaccessibility. Neglecting individual carotenoids, higher protein concentration correlated positively with carotenoid bioaccessibility (R = 0.57, p < 0.01), smaller micelle size (R = -0.83, p < 0.01), decreased repulsive forces (ζ-potential, R = -0.72, p < 0.01), and higher surface tension (R = 0.44, p < 0.01). In conclusion, proteins differentially affected carotenoid bioaccessibility during digestion depending on carotenoid and protein species, with both positive and negative interactions occurring.
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http://dx.doi.org/10.1039/d0fo00888eDOI Listing
June 2020

TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells.

Nat Commun 2020 01 23;11(1):454. Epub 2020 Jan 23.

Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, 57 Avenue Hippocrate B1.57.04, B-1200, Brussels, Belgium.

Acidosis, a common characteristic of the tumor microenvironment, is associated with alterations in metabolic preferences of cancer cells and progression of the disease. Here we identify the TGF-β2 isoform at the interface between these observations. We document that acidic pH promotes autocrine TGF-β2 signaling, which in turn favors the formation of lipid droplets (LD) that represent energy stores readily available to support anoikis resistance and cancer cell invasiveness. We find that, in cancer cells of various origins, acidosis-induced TGF-β2 activation promotes both partial epithelial-to-mesenchymal transition (EMT) and fatty acid metabolism, the latter supporting Smad2 acetylation. We show that upon TGF-β2 stimulation, PKC-zeta-mediated translocation of CD36 facilitates the uptake of fatty acids that are either stored as triglycerides in LD through DGAT1 or oxidized to generate ATP to fulfill immediate cellular needs. We also address how, by preventing fatty acid mobilization from LD, distant metastatic spreading may be inhibited.
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http://dx.doi.org/10.1038/s41467-019-14262-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978517PMC
January 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.
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http://dx.doi.org/10.1016/j.fsi.2019.06.011DOI Listing
September 2019

Whey protein isolate modulates beta-carotene bioaccessibility depending on gastro-intestinal digestion conditions.

Food Chem 2019 Sep 1;291:157-166. Epub 2019 Apr 1.

Luxembourg Institute of Health, Department of Population Health, Strassen, Luxembourg. Electronic address:

Carotenoids are lipophilic phytochemicals; their intake has been associated with reduced chronic diseases. However, their absorption depends on emulsification during digestion and incorporation into mixed micelles, requiring digestive enzymes, gastric peristalsis, bile, and dietary lipids. In this study, we investigated whether whey-protein-isolate (WPI), a commonly consumed protein source, can modulate β-carotene bioaccessibility in vitro, especially under incomplete digestive conditions, i.e. under low digestive enzyme concentrations. Thus, amounts of pepsin, pancreatin, bile, co-digested lipids and kinetic energy and gastric digestion time were modified, and WPI at concentrations equivalent to 0/25/50% of the protein recommended dietary allowance (approx. 60 g/d) were added to β-carotene dissolved in oil. WPI enhanced bioaccessibility by up to 20% (p < 0.001), especially under higher simulated peristalsis or reduced amount of dietary lipids. Conversely, they impaired bioaccessibility to one third (p < 0.001) under incomplete digestive conditions. WPI modulated β-carotene bioaccessibility depending on digestive conditions.
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http://dx.doi.org/10.1016/j.foodchem.2019.04.003DOI Listing
September 2019

Exploring the interactions between polyunsaturated fatty acids and cadmium in rainbow trout liver cells: a genetic and proteomic study.

Aquat Toxicol 2018 Dec 22;205:100-113. Epub 2018 Sep 22.

Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve, Belgium. Electronic address:

Polyunsaturated fatty acids (PUFAs) have key biological roles in fish cells. We recently showed that the phospholipid composition of rainbow trout liver cells (RTL-W1 cell line) modulates their tolerance to an acute cadmium (Cd) challenge. Here, we investigated (i) the extent to which PUFAs and Cd impact fatty acid homeostasis and metabolism in these cells and (ii) possible mechanisms by which specific PUFAs may confer cytoprotection against Cd. First, RTL-W1 cells were cultivated for one week in growth media spiked with 50 μmol L of either alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), linoleic acid (LA, 18:2n-6) or arachidonic acid (AA, 20:4n-6) in order to modulate their fatty acid profile. Then, the cells were challenged with Cd (0, 50 or 100 μmol L) for 24 h prior to assaying viability, fatty acid profile, intracellular Cd content, proteomic landscape and expression levels of genes involved in fatty acid metabolism, synthesis of PUFA-derived signalling molecules and stress response. We observed that the fatty acid supply and, to a lesser extent, the exposure to Cd influenced cellular fatty acid homeostasis and metabolism. The cellular fatty acid composition of fish liver cells modulated their tolerance to an acute Cd challenge. Enrichments in ALA, EPA, and, to a lesser extent, AA conferred cytoprotection while enrichment in LA had no impact on cell viability. The present study ruled out the possibility that cytoprotection reflects a decreased Cd burden. Our results rather suggest that the PUFA-derived cytoprotection against Cd occurs through a reduction of the oxidative stress induced by Cd and a differential induction of the eicosanoid cascade, with a possible role of peroxiredoxin and glutaredoxin (antioxidant enzymes) as well as cytosolic phospholipase A2 (enzyme initiating the eicosanoid cascade).
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http://dx.doi.org/10.1016/j.aquatox.2018.09.005DOI Listing
December 2018

Body lipid composition modulates acute cadmium toxicity in Daphnia magna adults and juveniles.

Chemosphere 2018 Aug 17;205:328-338. Epub 2018 Apr 17.

Laboratory of Environmental Toxicology and Aquatic Ecology, Environmental Toxicology Unit, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium. Electronic address:

Long chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA, 20:5n-3) affect zooplankton fitness and ability to cope with environmental stressors. However, the impact of LC-PUFAs on zooplankton sensitivity to chemical stressors is unknown. Here, we aimed to document the interaction between EPA and cadmium (Cd), as model chemical stressor, in Daphnia magna. A life-history experiment was performed in which daphnid neonates were raised into adulthood on three diets of different lipid composition: (i) algae mix; (ii) algae mix supplemented with control liposomes; (iii) algae mix supplemented with liposomes containing EPA. Juveniles (3rd, 4th and 5th brood) released by daphnids during this life-history experiment were sampled, challenged with Cd during 48 h and their immobility was assessed. At the end of this life-history experiment, another immobilisation test was performed with adults from each treatment. Daphnids absorbed, incorporated and transferred ingested EPA to their offspring. Liposome feeding increased adult tolerance to Cd. The presence of EPA in liposomes did not increase adult tolerance to Cd. Offspring's tolerance to Cd was influenced by the brood number and the maternal diet. It was positively correlated with the PUFA level in body neutral lipids, especially alpha-linolenic acid (ALA, 18:3n-3) and negatively correlated with the saturated fatty acid level in body neutral lipids, especially stearic acid (18:0). Overall, these results emphasize the importance of dietary lipids and maternal transfer of body lipids in D. magna sensitivity to Cd and highlight the need to take into account these parameters in ecotoxicological studies and risk assessment.
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http://dx.doi.org/10.1016/j.chemosphere.2018.04.091DOI Listing
August 2018

Transcriptional effects of phospholipid fatty acid profile on rainbow trout liver cells exposed to methylmercury.

Aquat Toxicol 2018 Jun 22;199:174-187. Epub 2018 Mar 22.

Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve, Belgium.

Lipids, and their constitutive fatty acids, are key nutrients for fish health as they provide energy, maintain cell structure, are precursors of signalling molecules and act as nuclear receptor ligands. These specific roles may be of crucial importance in a context of exposure to pollutants. We recently showed that the fatty acid profile of rainbow trout liver cell phospholipids modulates sensitivity to an acute methylmercury challenge. In order to investigate mechanisms of effects, we herein tested whether specific polyunsaturated fatty acids (PUFAs) may protect cells from methylmercury through decreasing intracellular mercury accumulation and/or enhancing cellular defences (e.g. via modulation of gene expression patterns). We also investigated the inverse relationship and assessed the impact of methylmercury on cellular fatty acid metabolism. To do so, the fatty acid composition of rainbow trout liver cell phospholipids was first modified by incubating them in a medium enriched in a specific PUFA from either the n-3 family (alpha-linolenic acid, ALA; eicosapentaenoic acid, EPA) or the n-6 family (linoleic acid, LA; arachidonic acid, AA). Cells were then exposed to methylmercury (0.15 or 0.50 μM) for 24 h and sampled thereafter for assessing phospholipid fatty acid profile, intracellular total mercury burden, and expression pattern of genes involved in fatty acid metabolism, synthesis of PUFA-derived signalling molecules and stress response. We observed that cells incorporated the given PUFA and some biotransformation products in their phospholipids. Methylmercury had few impacts on this cellular phospholipid composition. None of the PUFA enrichments affected the cellular mercury burden, suggesting that the previously observed cytoprotection conferred by ALA and EPA was not linked to a global decrease in cellular accumulation of mercury. Fatty acid enrichments and methylmercury exposure both modulated gene expression patterns. Genes involved in the synthesis of PUFA-derived signalling molecules, in stress response and the orphan cytochrome P450 20A1 were identified as possible sites of interaction between fatty acids and methylmercury in rainbow trout liver cells.
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http://dx.doi.org/10.1016/j.aquatox.2018.03.025DOI Listing
June 2018

Environmentally-realistic concentration of cadmium combined with polyunsaturated fatty acids enriched diets modulated non-specific immunity in rainbow trout.

Aquat Toxicol 2018 Mar 3;196:104-116. Epub 2018 Feb 3.

Research Unit in Environmental and Evolutionary Biology (URBE), University of Namur (UNamur), 5000 Namur, Belgium.

Nutrition is crucial to grow healthy fish particularly in a context of pollution, overcrowding and pathogen risks. Nowadays, the search for food components able to improve fish health is increasingly developing. Here, the influence of four dietary polyunsaturated fatty acids (PUFAs) that are alpha-linolenic acid (ALA, 18:3n-3), linoleic acid (LA, 18:2n-6), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) on the sensitivity of rainbow trout (Oncorhynchus mykiss) juveniles to environmentally realistic cadmium (Cd, 0.3 μg/L) concentration was investigated. Fish diets were designed to ensure the specific abundance of one of these individual PUFAs, and were given for a 4-week pre-conditioning period followed by a 6-week Cd exposure period. Focus was put on growth performance and immune responses following a short (24 h) and a long-term (6 weeks) Cd exposure. For each experimental condition, some fish were submitted to a bacterial challenge (24 h) with Aeromonas salmonicida achromogenes at the end of Cd conditioning period. DHA-enriched diet improved growth performances as compared to LA-enriched diet, but also increased ROS production (after short-term exposure to Cd) that could lead to a higher inflammation status, and some immunity-related genes (at short and long-term exposure). We notably highlighted the fact that even a low, environmentally-realistic concentration, Cd can strongly impact the immune system of rainbow trout, and that specific dietary PUFA enrichment strategies can improve growth performance (DHA-enriched diet), provide protection against oxidative stress (ALA- and EPA-enriched diet) and stimulate non-specific immunity.
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http://dx.doi.org/10.1016/j.aquatox.2018.01.012DOI Listing
March 2018

Implication of trans-11,trans-13 conjugated linoleic acid in the development of hepatic steatosis.

PLoS One 2018 1;13(2):e0192447. Epub 2018 Feb 1.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.

Scope: Conjugated linoleic acids are linoleic acid isomers found in the diet that can also be produced through bacterial metabolism of polyunsaturated fatty acids. Our objective was to evaluate the contribution of fatty acid metabolites produced from polyunsaturated fatty acids by the gut microbiota in vivo to regulation of hepatic lipid metabolism and steatosis.

Methods And Results: In mice with depleted n-3 polyunsaturated fatty acids, we observed an accumulation of trans-11,trans-13 CLA and cis-9,cis-11 conjugated linoleic acids in the liver tissue that were associated with an increased triglyceride content and expression of lipogenic genes. We used an in vitro model to evaluate the impact of these two conjugated linoleic acids on hepatic lipid metabolism. In HepG2 cells, we observed that only trans-11,trans-13 conjugated linoleic acids recapitulated triglyceride accumulation and increased lipogenic gene expression, which is a phenomenon that may implicate the nuclear factors sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP).

Conclusion: The trans-11,trans-13 conjugated linoleic acids can stimulate hepatic lipogenesis, which supports the conclusion that gut microbiota and related metabolites should be considered in the treatment of non-alcoholic liver disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192447PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794163PMC
April 2018

Relative influence of dietary protein and energy contents on lysine requirements and voluntary feed intake of rainbow trout fry.

Br J Nutr 2018 01 10;119(1):42-56. Epub 2017 Dec 10.

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

The effect of dietary digestible protein (DP) and/or digestible energy (DE) levels on lysine (Lys) requirements, Lys utilisation efficiency and voluntary feed intake (VFI) were studied in rainbow trout fry when Lys was the first limiting indispensable amino acid or in excess in the diet. Two trials were conducted at 11·6°C with eighty-one experimental diets, containing 280 g DP/kg DM (low protein (LP), trial 1), 600 g DP/kg DM (high protein (HP), trial 1) or 440 g DP/kg DM (medium protein (MP), trial 2), 17 MJ DE/kg (low energy (LE)), 19·5 MJ DE/kg (medium energy (ME)) or 22 MJ DE/kg (high energy (HE)), and nine Lys levels from deeply deficient to large excess (2·3-36 g/kg DM). Each diet was given to apparent satiety to one group of fifty fry (initial body weight 0·85 g) for 24 (MP diets, trial 2) or 30 (LP and HP diets, trial 1) feeding days. Based on N gain data fitted with the broken-line model, the relative Lys requirement was significantly different with the dietary DP level, from 13·3-15·7 to 22·9-26·5 g/kg DM for LP and HP diets, respectively, but did not significantly change with the DE level for a same protein level. The Lys utilisation efficiency for protein growth above maintenance was constant across diets, suggesting no effect of either dietary DE or DP levels. In Lys excess, the VFI was markedly decreased by the DP level but not by the extra DE supply. Our results suggest that the relative Lys need is best expressed in terms of percentage of protein content for optimum fish feed formulation, at least in rainbow trout fry.
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http://dx.doi.org/10.1017/S0007114517003300DOI Listing
January 2018

Recent advances on bioactivities of black rice.

Curr Opin Clin Nutr Metab Care 2017 Nov;20(6):470-476

aCollege of Biotechnology, Universidade Federal do Pará & Centre for Valorization of Amazonian Bioactive Compounds, Belém-PA, Brazil bCenter of Investigation in Clinical Nutrition, Université catholique de Louvain, Louvain-la-Neuve, Belgium cLife Sciences Institute, Université catholique de Louvain, Louvain-la-Neuve, Belgium dPharmacognosy research group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.

Purpose Of Review: Black rice has been consumed for centuries in Asian countries such as China, Korea or Japan. Nowadays, extracts and derivatives are considered as beneficial functional foods because of their high content in several bioactive molecules such as anthocyanins, other phenolics and terpenoids. The purpose of this review is to summarize and discuss recent developments on black rice bioactivities.

Recent Findings: Some sterols and triterpenoids with potential anticancer properties already tested in vitro and in vivo have been isolated and identified from bran extracts of black rice. Protection against osteoporosis has been suggested for the first time for black rice extracts. Because of its antioxidant and anti-inflammatory properties, black rice also protects liver and kidney from injuries. One clinical study reported the interest of black rice in case of alcohol withdrawal.

Summary: Several advances have been recently achieved on the understanding of the potential biological effects of black rice and its derivatives. They further confirm that black rice should be considered as a promising source of health-promoting functional foods targeting a large set of noninfectious diseases. However, more clinical studies are needed to support the findings highlighted in this review.
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http://dx.doi.org/10.1097/MCO.0000000000000417DOI Listing
November 2017

PDGF-induced fibroblast growth requires monounsaturated fatty acid production by stearoyl-CoA desaturase.

FEBS Open Bio 2017 Mar 2;7(3):414-423. Epub 2017 Feb 2.

de Duve Institute MEXP unit Université catholique de Louvain Brussels Belgium.

Stearoyl-coenzyme A desaturase (SCD) catalyzes the Δ9-cis desaturation of saturated fatty acids (SFA) to generate monounsaturated fatty acids (MUFA). This enzyme is highly up-regulated by platelet-derived growth factor (PDGF) in human fibroblasts. Accordingly, the analysis of cellular fatty acids by gas chromatography showed that PDGF significantly increased the proportion of MUFA, particularly palmitoleate, in cellular lipids. To further analyze the role of SCD in fibroblasts, we used small hairpin RNA targeting SCD (shSCD), which decreased the MUFA content. SCD down-regulation blunted the proliferation of fibroblasts in response to PDGF. This was confirmed using a pharmacological inhibitor of SCD. In addition, proliferation was blocked by palmitate and stearate (two SCD substrates) but not by palmitoleate and oleate (two SCD products). In the presence of an equal amount of oleate, palmitate had no effect on cell proliferation. SCD inhibition or down-regulation did not decrease PDGF receptor activity or signaling. However, by measuring plasma membrane lipid lateral diffusion by fluorescence recovery after photobleaching, we showed that the modulation of the MUFA/SFA ratio by PDGF and SCD inhibitor was related to modifications of membrane fluidity. Altogether, our data suggest that SCD is required for the response of normal fibroblasts to growth factors.
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http://dx.doi.org/10.1002/2211-5463.12194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337901PMC
March 2017

Pentacyclic Triterpene Bioavailability: An Overview of In Vitro and In Vivo Studies.

Molecules 2017 Mar 4;22(3). Epub 2017 Mar 4.

Department of Environmental Research and Innovation, Luxembourg Institute of Science and Technology, L-4422 Belvaux, Luxembourg.

Pentacyclic triterpenes are naturally found in a great variety of fruits, vegetables and medicinal plants and are therefore part of the human diet. The beneficial health effects of edible and medicinal plants have partly been associated with their triterpene content, but the in vivo efficacy in humans depends on many factors, including absorption and metabolism. This review presents an overview of in vitro and in vivo studies that were carried out to determine the bioavailability of pentacyclic triterpenes and highlights the efforts that have been performed to improve the dissolution properties and absorption of these compounds. As plant matrices play a critical role in triterpene bioaccessibility, this review covers literature data on the bioavailability of pentacyclic triterpenes ingested either from foods and medicinal plants or in their free form.
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http://dx.doi.org/10.3390/molecules22030400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155290PMC
March 2017

A n-3 PUFA depletion applied to rainbow trout fry (Oncorhynchus mykiss) does not modulate its subsequent lipid bioconversion capacity.

Br J Nutr 2017 01 23;117(2):187-199. Epub 2017 Jan 23.

1Institut des Sciences de la Vie,Université catholique de Louvain,Croix du Sud,2/L7.05.08,1348 Louvain-la-Neuve,Belgium.

Nutritional strategies are currently developed to produce farmed fish rich in n-3 long-chain PUFA (LC-PUFA) whilst replacing fish oil by plant-derived oils in aquafeeds. The optimisation of such strategies requires a thorough understanding of fish lipid metabolism and its nutritional modulation. The present study evaluated the fatty acid bioconversion capacity of rainbow trout (Oncorhynchus mykiss) fry previously depleted in n-3 PUFA through a 60-d pre-experimental feeding period with a sunflower oil-based diet (SO) followed by a 36-d experimental period during which fish were fed either a linseed oil-based diet (LO) (this treatment being called SO/LO) or a fish oil-based diet (FO) (this treatment being called SO/FO). These treatments were compared with fish continuously fed on SO, LO or FO for 96 d. At the end of the 36-d experimental period, SO/LO and SO/FO fish recovered >80 % of the n-3 LC-PUFA reported for LO and FO fish, respectively. Fish fed on LO showed high apparent in vivo elongation and desaturation activities along the n-3 biosynthesis pathway. However, at the end of the experimental period, no impact of the fish n-3 PUFA depletion was observed on apparent in vivo elongation and desaturation activities of SO/LO fish as compared with LO fish. In contrast, the fish n-3 PUFA depletion negatively modulated the n-6 PUFA bioconversion capacity of fish in terms of reduced apparent in vivo elongation and desaturation activities. The effects were similar after 10 or 36 d of the experimental period, indicating the absence of short-term effects.
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http://dx.doi.org/10.1017/S0007114516004487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314960PMC
January 2017

Temperature Increase Negatively Affects the Fatty Acid Bioconversion Capacity of Rainbow Trout (Oncorhynchus mykiss) Fed a Linseed Oil-Based Diet.

PLoS One 2016 13;11(10):e0164478. Epub 2016 Oct 13.

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

Aquaculture is meant to provide fish rich in omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA). This objective must be reached despite (1) the necessity to replace the finite and limited fish oil in feed production and (2) the increased temperature of the supply water induced by the global warming. The objective of the present paper was to determine to what extent increased water temperature influences the fatty acid bioconversion capacity of rainbow trout (Oncorhynchus mykiss) fed a plant-derived diet. Fish were fed two diets formulated with fish oil (FO) or linseed oil (LO) as only added lipid source at the optimal water temperature of 15°C or at the increased water temperature of 19°C for 60 days. We observed that a temperature increase close to the upper limit of the species temperature tolerance range negatively affected the feed efficiency of rainbow trout fed LO despite a higher feed intake. The negative impact of increased water temperature on fatty acid bioconversion capacity appeared also to be quite clear considering the reduced expression of fatty acid desaturase 2 in liver and intestine and the reduced Δ6 desaturase enzymatic activity in intestinal microsomes. The present results also highlighted a negative impact of increased temperature on the apparent in vivo enzymatic activity of Δ5 and Δ6 desaturases of fish fed LO. Interestingly, this last parameter appeared less affected than those mentioned above. This study highlights that the increased temperature that rainbow trout may face due to global warming could reduce their fatty acid bioconversion capacity. The unavoidable replacement of finite fish oil by more sustainable, readily available and economically viable alternative lipid sources in aquaculture feeds should take this undeniable environmental issue on aquaculture productivity into account.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063364PMC
May 2017

The fatty acid profile of rainbow trout liver cells modulates their tolerance to methylmercury and cadmium.

Aquat Toxicol 2016 Aug 23;177:171-81. Epub 2016 May 23.

Institute of Life Sciences, Université catholique de Louvain, Place Croix du Sud 2/L7.05.08, B-1348 Louvain-la-Neuve, Belgium.

The polyunsaturated fatty acid (PUFA) composition of fish tissues, which generally reflects that of the diet, affects various cellular properties such as membrane structure and fluidity, energy metabolism and susceptibility to oxidative stress. Since these cellular parameters can play an important role in the cellular response to organic and inorganic pollutants, a variation of the PUFA supply might modify the toxicity induced by such xenobiotics. In this work, we investigated whether the cellular fatty acid profile has an impact on the in vitro cell sensitivity to two environmental pollutants: methylmercury and cadmium. Firstly, the fatty acid composition of the rainbow trout liver cell line RTL-W1 was modified by enriching the growth medium with either alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), linoleic acid (LA, 18:2n-6), arachidonic acid (AA, 20:4n-6) or docosapentaenoic acid (DPA, 22:5n-6). These modified cells and their control (no PUFA enrichment) were then challenged for 24h with increasing concentrations of methylmercury or cadmium. We observed that (i) the phospholipid composition of the RTL-W1 cells was profoundly modulated by changing the PUFA content of the growth medium: major modifications were a high incorporation of the supplemented PUFA in the cellular phospholipids, the appearance of direct elongation and desaturation metabolites in the cellular phospholipids as well as a change in the gross phospholipid composition (PUFA and monounsaturated fatty acid (MUFA) levels and n-3/n-6 ratio); (ii) ALA, EPA and DPA enrichment significantly protected the RTL-W1 cells against both methylmercury and cadmium; (iv) DHA enrichment significantly protected the cells against cadmium but not methylmercury; (v) AA and LA enrichment had no impact on the cell tolerance to both methylmercury and cadmium; (vi) the abundance of 20:3n-6, a metabolite of the n-6 biotransformation pathway, in phospholipids was negatively correlated to the cell tolerance to both methylmercury and cadmium. Overall, our results highlighted the importance of the fatty acid supply on the tolerance of fish liver cells to methylmercury and cadmium.
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http://dx.doi.org/10.1016/j.aquatox.2016.05.023DOI Listing
August 2016

Multifunctional oxidosqualene cyclases and cytochrome P450 involved in the biosynthesis of apple fruit triterpenic acids.

New Phytol 2016 09 23;211(4):1279-94. Epub 2016 May 23.

The New Zealand Institute for Plant & Food Research Limited, Mt Albert Research Centre, Private Bag 92 169, Auckland, 1142, New Zealand.

Apple (Malus × domestica) accumulates bioactive ursane-, oleanane-, and lupane-type triterpenes in its fruit cuticle, but their biosynthetic pathway is still poorly understood. We used a homology-based approach to identify and functionally characterize two new oxidosqualene cyclases (MdOSC4 and MdOSC5) and one cytochrome P450 (CYP716A175). The gene expression patterns of these enzymes and of previously described oxidosqualene cyclases were further studied in 20 apple cultivars with contrasting triterpene profiles. MdOSC4 encodes a multifunctional oxidosqualene cyclase producing an oleanane-type triterpene, putatively identified as germanicol, as well as β-amyrin and lupeol, in the proportion 82 : 14 : 4. MdOSC5 cyclizes 2,3-oxidosqualene into lupeol and β-amyrin at a ratio of 95 : 5. CYP716A175 catalyses the C-28 oxidation of α-amyrin, β-amyrin, lupeol and germanicol, producing ursolic acid, oleanolic acid, betulinic acid, and putatively morolic acid. The gene expression of MdOSC1 was linked to the concentrations of ursolic and oleanolic acid, whereas the expression of MdOSC5 was correlated with the concentrations of betulinic acid and its caffeate derivatives. Two new multifuntional triterpene synthases as well as a multifunctional triterpene C-28 oxidase were identified in Malus × domestica. This study also suggests that MdOSC1 and MdOSC5 are key genes in apple fruit triterpene biosynthesis.
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http://dx.doi.org/10.1111/nph.13996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089662PMC
September 2016
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