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Article ; Online: Adipose tissue angiogenesis genes are down-regulated by grape polyphenols supplementation during a human overfeeding trial.

Delage, Pauline / Ségrestin, Bérénice / Seyssel, Kévin / Chanon, Stéphanie / Vieille-Marchiset, Aurélie / Durand, Annie / Nemeth, Angéline / Métairon, Sylviane / Charpagne, Aline / Descombes, Patrick / Hager, Jörg / Laville, Martine / Vidal, Hubert / Meugnier, Emmanuelle

The Journal of nutritional biochemistry

2023 Volume 117, Page(s) 109334

Abstract: The adaptive response to overfeeding is associated with profound modifications of gene expression in adipose tissue to support lipid storage and weight gain. The objective of this study was to assess in healthy lean men whether a supplementation with ... ...

Abstract	The adaptive response to overfeeding is associated with profound modifications of gene expression in adipose tissue to support lipid storage and weight gain. The objective of this study was to assess in healthy lean men whether a supplementation with polyphenols could interact with these molecular adaptations. Abdominal subcutaneous adipose tissue biopsies were sampled from 42 subjects participating to an overfeeding protocol providing an excess of 50% of their total energy expenditure for 31 days, and who were supplemented with 2 g/day of grape polyphenols or a placebo. Gene expression profiling was performed by RNA sequencing. Overfeeding led to a modification of the expression of 163 and 352 genes in the placebo and polyphenol groups, respectively. The GO functions of these genes were mostly involved in lipid metabolism, followed by genes involved in adipose tissue remodeling and expansion. In response to overfeeding, 812 genes were differentially regulated between groups. Among them, a set of 41 genes were related to angiogenesis and were down-regulated in the polyphenol group. Immunohistochemistry targeting PECAM1, as endothelial cell marker, confirmed reduced angiogenesis in this group. Finally, quercetin and isorhamnetin, two polyphenol species enriched in the plasma of the volunteers submitted to the polyphenols, were found to inhibit human umbilical vein endothelial cells migration in vitro. Polyphenol supplementation do not prevent the regulation of genes related to lipid metabolism in human adipose tissue during overfeeding, but impact the angiogenesis pathways. This may potentially contribute to a protection against adipose tissue expansion during dynamic phase of weight gain.
MeSH term(s)	Male ; Humans ; Vitis ; Endothelial Cells/metabolism ; Adipose Tissue/metabolism ; Obesity/metabolism ; Weight Gain/physiology ; Dietary Supplements ; Polyphenols/pharmacology ; Polyphenols/metabolism
Chemical Substances	Polyphenols
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2023.109334
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Article ; Online: Adipose tissue angiogenesis genes are down-regulated by grape polyphenols supplementation during a human overfeeding trial

The Journal of Nutritional Biochemistry. 2023 July, v. 117 p.109334-

2023

Abstract	The adaptive response to overfeeding is associated with profound modifications of gene expression in adipose tissue to support lipid storage and weight gain. The objective of this study was to assess in healthy lean men whether a supplementation with polyphenols could interact with these molecular adaptations. Abdominal subcutaneous adipose tissue biopsies were sampled from 42 subjects participating to an overfeeding protocol providing an excess of 50% of their total energy expenditure for 31 days, and who were supplemented with 2 g/day of grape polyphenols or a placebo. Gene expression profiling was performed by RNA sequencing. Overfeeding led to a modification of the expression of 163 and 352 genes in the placebo and polyphenol groups, respectively. The GO functions of these genes were mostly involved in lipid metabolism, followed by genes involved in adipose tissue remodeling and expansion. In response to overfeeding, 812 genes were differentially regulated between groups. Among them, a set of 41 genes were related to angiogenesis and were down-regulated in the polyphenol group. Immunohistochemistry targeting PECAM1, as endothelial cell marker, confirmed reduced angiogenesis in this group. Finally, quercetin and isorhamnetin, two polyphenol species enriched in the plasma of the volunteers submitted to the polyphenols, were found to inhibit human umbilical vein endothelial cells migration in vitro. Polyphenol supplementation do not prevent the regulation of genes related to lipid metabolism in human adipose tissue during overfeeding, but impact the angiogenesis pathways. This may potentially contribute to a protection against adipose tissue expansion during dynamic phase of weight gain.
Keywords	RNA ; adipose tissue ; angiogenesis ; endothelial cells ; energy expenditure ; gene expression ; grapes ; humans ; immunohistochemistry ; isorhamnetin ; lipid metabolism ; lipids ; placebos ; polyphenols ; quercetin ; weight gain ; Human randomized trial ; Overfeeding ; Nutrigenomics
Language	English
Dates of publication	2023-07
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2023.109334
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Article ; Online: A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women.

Boulet, Marie Michèle / Calzada, Catherine / Pettazzoni, Magali / Lelekov-Boissard, Taïssia / Buisson, Charline / Di Filippo, Mathilde / Durand, Annie / Lambert-Porcheron, Stéphanie / Nazare, Julie-Anne / Moulin, Philippe / Michalski, Marie-Caroline / Cheillan, David

Biochimie

2022

Abstract: Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and ... ...

Abstract	Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.
Language	English
Publishing date	2022-07-08
Publishing country	France
Document type	Journal Article
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2022.07.003
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Article: A meal rich in palm oil or butter modifies the sphingolipid profile of postprandial triglyceride-rich lipoproteins from type 2 diabetic women

Biochimie. 2022 July 05,

2022

Abstract	Elevated concentrations of triglyceride-rich lipoproteins (TGRL) in the fasting and postprandial states are risk factors for cardiovascular events, especially in type 2 diabetes (T2D). T2D modifies the lipid composition of plasma and lipoproteins and some sphingolipids (SP) have been validated as potent predictive biomarkers of cardiovascular disease occurrence. The main objectives of the present study were to characterize the plasma SP profile in fasting T2D patients and to determine whether SP are modified in postprandial TGRL from these patients compared to fasting TGRL. In a randomized parallel-group study, 30 T2D women ingested a breakfast including 20g lipids from either hazelnut cocoa palm oil-rich spread (Palm Nut) or Butter. Plasma was collected and TGRL were isolated by ultracentrifugation at fasting and 4h after the meal. Fasting samples of 6 control subjects from another cohort were analyzed for comparison. SP were analyzed by tandem mass spectrometry. Plasma from fasting T2D patients had higher ceramide (Cer) and ganglioside GM3 concentrations, and lower concentrations of sphingosylphosphorylcholine vs healthy subjects. In postprandial TGRL from T2D patients compared to those in the fasting state, Cer concentrations and especially C16:0, C24:1 and C24:0 molecular species, increased after the Palm Nut or Butter breakfast. A positive correlation was observed in the Palm Nut group between changes (Δ4h-fasting) of summed C16:0+C22:0+C24:1+C24:0 Cer concentrations in TGRL, and changes in plasma TG, TGRL-TG and TGRL-C16:0 concentrations. Altogether in T2D, the altered profile of plasma SP and the increased Cer concentrations in postprandial TGRL could contribute to the increased atherogenicity of TGRL.
Keywords	biomarkers ; breakfast ; butter ; cardiovascular diseases ; ceramides ; disease occurrence ; fasting ; gangliosides ; hazelnuts ; lipid composition ; lipoproteins ; noninsulin-dependent diabetes mellitus ; palm oils ; tandem mass spectrometry ; ultracentrifugation
Language	English
Dates of publication	2022-0705
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	120345-9
ISSN	0300-9084
ISSN	0300-9084
DOI	10.1016/j.biochi.2022.07.003
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Article ; Online: Homogeneous triacylglycerol tracers have an impact on the thermal and structural properties of dietary fat and its lipolysis rate under simulated physiological conditions.

Danthine, Sabine / Vors, Cécile / Agopian, Damien / Durand, Annie / Guyon, Romain / Carriere, Frédéric / Knibbe, Carole / Létisse, Marion / Michalski, Marie-Caroline

Chemistry and physics of lipids

2019 Volume 225, Page(s) 104815

Abstract: Dietary fats are present in the diet under different types of structures, such as spread vs emulsions (notably in processed foods and enteral formula), and interest is growing regarding their digestion and intestinal absorption. In clinical trials, there ...

Abstract	Dietary fats are present in the diet under different types of structures, such as spread vs emulsions (notably in processed foods and enteral formula), and interest is growing regarding their digestion and intestinal absorption. In clinical trials, there is often a need to add stable isotope-labeled triacylglycerols (TAGs) as tracers to the ingested fat in order to track its intestinal absorption and further metabolic fate. Because most TAG tracers contain saturated fatty acids, they may modify the physicochemical properties of the ingested labeled fat and thereby its digestion. However, the actual impact of tracer addition on fat crystalline properties and lipolysis by digestive lipases still deserves to be explored. In this context, we monitored the thermal and polymorphic behavior of anhydrous milk fat (AMF) enriched in homogeneous TAGs tracers and further compared it with the native AMF using differential scanning calorimetry and power X-ray diffraction. As tracers, we used a mixture of tripalmitin, triolein and tricaprylin at 2 different concentrations (1.5 and 5.7 wt%, which have been used in clinical trials). The addition of TAG tracers modified the AMF melting profile, especially at the highest tested concentration (5.7 wt%). Both AMF and AMF enriched with 1.5 wt% tracers were completely melted around 37 °C, i.e. close to the body temperature, while the AMF enriched with 5.7 wt% tracers remained partially crystallized at this temperature. Similar trends were observed in both bulk and emulsified systems. Moreover, the kinetics of AMF polymorphic transformation was modified in the presence of tracers. While only β' form was observed in the native AMF, the β-form was clearly detected in the AMF containing 5.7 wt% tracers. We further tested the impact of tracers on the lipolysis of AMF in bulk using a static in vitro model of duodenal digestion. Lipolysis of AMF enriched with 5.7 wt% tracers was delayed compared with that of AMF and AMF enriched with 1.5 wt% tracers. Therefore, low amounts of TAG tracers including tripalmitin do not have a high impact on fat digestion, but one has to be cautious when using higher amounts of these tracers.
MeSH term(s)	Dietary Fats ; Lipolysis ; Molecular Structure ; Temperature ; Triglycerides/chemistry
Chemical Substances	Dietary Fats ; Triglycerides
Language	English
Publishing date	2019-09-05
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	213869-4
ISSN	1873-2941 ; 0009-3084
ISSN (online)	1873-2941
ISSN	0009-3084
DOI	10.1016/j.chemphyslip.2019.104815
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Article: Homogeneous triacylglycerol tracers have an impact on the thermal and structural properties of dietary fat and its lipolysis rate under simulated physiological conditions

Danthine, Sabine / Agopian, Damien / Carriere, frédéric / Durand, Annie / Guyon, romain / Knibbe, carole / Letisse, Marion / Michalski, Marie-Caroline / Vors, Cécile

Chemistry and physics of lipids. 2019 Sept. 01,

2019

Abstract	Dietary fats are present in the diet under different types of structures, such as spread vs emulsions (notably in processed foods and enteral formula), and interest is growing regarding their digestion and intestinal absorption. In clinical trials, there is often a need to add stable isotope-labeled triacylglycerols (TAGs) as tracers to the ingested fat in order to track its intestinal absorption and further metabolic fate. Because most TAG tracers contain saturated fatty acids, they may modify the physicochemical properties of the ingested labeled fat and thereby its digestion. However, the actual impact of tracer addition on fat crystalline properties and lipolysis by digestive lipases still deserves to be explored. In this context, we monitored the thermal and polymorphic behavior of anhydrous milk fat (AMF) enriched in homogeneous TAGs tracers and further compared it to the native AMF using differential scanning calorimetry and power X-ray diffraction. As tracers, we used a mixture of tripalmitin, triolein and tricaprylin at 2 different concentrations (of 1.5 and 5.7 wt%, which have been used in clinical trials). The addition of TAG tracers modified the AMF melting profile, especially at the highest tested concentration (5.7% wt%). Both AMF and AMF enriched with 1.5 wt% tracers were completely melted at around 37 °C, i.e. close to the body temperature, while the AMF enriched with 5.7 wt% tracers remained partially crystallized at this temperature. Similar trends were observed in both bulk and emulsified systems. Moreover, the kinetics of AMF polymorphic transformation was modified in the presence of tracers. While only β’ form was observed in the native AMF, the β-form was clearly detected in the AMF containing 5.7 wt% tracers. We further tested the impact of tracers on the lipolysis of AMF in bulk using a static in vitro model of duodenal digestion. Lipolysis of AMF enriched with 5.7 wt% tracers was delayed compared that of AMF and AMF enriched with 1.5 wt% tracers. Therefore, low amounts of TAG tracers including tripalmitin do not have a high impact on fat digestion, but one has to be cautious when using higher amounts of these tracers.
Keywords	anhydrous milk fat ; body temperature ; carboxylic ester hydrolases ; clinical trials ; crystallization ; dietary fat ; differential scanning calorimetry ; digestion ; emulsions ; intestinal absorption ; isotope labeling ; lipolysis ; melting ; models ; physicochemical properties ; processed foods ; saturated fatty acids ; triolein ; tripalmitin ; X-ray diffraction
Language	English
Dates of publication	2019-0901
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	213869-4
ISSN	1873-2941 ; 0009-3084
ISSN (online)	1873-2941
ISSN	0009-3084
DOI	10.1016/j.chemphyslip.2019.104815
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Article ; Online: ANT2-Mediated ATP Import into Mitochondria Protects against Hypoxia Lethal Injury.

Gouriou, Yves / Alam, Muhammad Rizwan / Harhous, Zeina / Crola Da Silva, Claire / Baetz, Delphine Baetz / Badawi, Sally / Lefai, Etienne / Rieusset, Jennifer / Durand, Annie / Harisseh, Rania / Gharib, Abdallah / Ovize, Michel / Bidaux, Gabriel

Cells

2020 Volume 9, Issue 12

Abstract: Following a prolonged exposure to hypoxia-reoxygenation, a partial disruption of the ER-mitochondria tethering by mitofusin 2 (MFN2) knock-down decreases the ... ...

Abstract	Following a prolonged exposure to hypoxia-reoxygenation, a partial disruption of the ER-mitochondria tethering by mitofusin 2 (MFN2) knock-down decreases the Ca
MeSH term(s)	Adenine Nucleotide Translocator 2/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Calcium/metabolism ; Cell Death/physiology ; Cell Line ; Hypoxia/metabolism ; Membrane Potential, Mitochondrial/physiology ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/metabolism ; Mitochondrial Membranes/metabolism ; Myocytes, Cardiac/metabolism ; Rats
Chemical Substances	Adenine Nucleotide Translocator 2 ; Mitochondrial Membrane Transport Proteins ; Adenosine Triphosphate (8L70Q75FXE) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-11-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9122542
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Article ; Online: Human milk pasteurisation reduces pre-lipolysis but not digestive lipolysis and moderately decreases intestinal lipid uptake in a combination of preterm infant in vitro models.

Vincent, Marine / Ménard, Olivia / Etienne, Julie / Ossemond, Jordane / Durand, Annie / Buffin, Rachel / Loizon, Emmanuelle / Meugnier, Emmanuelle / Deglaire, Amélie / Dupont, Didier / Picaud, Jean-Charles / Knibbe, Carole / Michalski, Marie-Caroline / Penhoat, Armelle

Food chemistry

2020 Volume 329, Page(s) 126927

Abstract: Donor human milk, pasteurised for safety reasons, is the first alternative for feeding preterm infants when mothers' own milk is unavailable. Breastmilk pasteurisation impact on lipid digestion and absorption was evaluated by a static in vitro digestion ... ...

Abstract	Donor human milk, pasteurised for safety reasons, is the first alternative for feeding preterm infants when mothers' own milk is unavailable. Breastmilk pasteurisation impact on lipid digestion and absorption was evaluated by a static in vitro digestion model for preterm infants coupled with intestinal absorption using Caco-2/TC7 cells. Lipid absorption was quantified by digital image analysis of lipid droplets, by measurement of basolateral triglyceride concentration and by analysing the expression of major genes involved. After in vitro digestion, lipolysis extent was 13% lower in pasteurised human milk (PHM) than in raw human milk (RHM). In Caco-2/TC7 cells, the number of lipid droplets was identical for both milk types, while the mean droplet area was 17% smaller with PHM. Altogether, pasteurisation decreased the pre-lipolysis of human milk. This initial difference in free fatty acid amount was only partially buffered by the subsequent processes of in vitro digestion and cellular lipid absorption.
MeSH term(s)	Cell Line ; Digestion ; Humans ; Infant, Newborn ; Infant, Premature ; Intestinal Mucosa ; Intestines ; Lipids/chemistry ; Lipolysis ; Milk, Human/chemistry ; Pasteurization
Chemical Substances	Lipids
Language	English
Publishing date	2020-05-06
Publishing country	England
Document type	Journal Article
ZDB-ID	243123-3
ISSN	1873-7072 ; 0308-8146
ISSN (online)	1873-7072
ISSN	0308-8146
DOI	10.1016/j.foodchem.2020.126927
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Article ; Online: Endoplasmic reticulum stress contributes to heart protection induced by cyclophilin D inhibition.

Belaidi, Elise / Decorps, Johanna / Augeul, Lionel / Durand, Annie / Ovize, Michel

Basic research in cardiology

2013 Volume 108, Issue 4, Page(s) 363

Abstract: Preventing cyclophilin D (cypD) translocation to the inner mitochondrial membrane can limit lethal reperfusion injury through the inhibition of the opening of the mitochondrial permeability transition pore. Inhibition or loss of function of cypD may also ...

Abstract	Preventing cyclophilin D (cypD) translocation to the inner mitochondrial membrane can limit lethal reperfusion injury through the inhibition of the opening of the mitochondrial permeability transition pore. Inhibition or loss of function of cypD may also result into an endoplasmic reticulum (ER) stress that has been shown to alter cell survival. We therefore questioned whether ER stress might play a role in the protection induced by CypD deficiency or inhibition. CypD-KO and NIM811 (a CypD inhibitor)-treated mice were subjected to a prolonged ischemia-reperfusion (I/R). Area at risk and infarct size was measured using blue dye and triphenyltetrazolium chloride staining. ER stress markers were measured in the hearts during the reperfusion phase. As expected, cypD-KO mice exhibited a decreased infarct size when compared to wild-type mice (8 ± 1 vs. 20 ± 4% of left ventricular weight; p < 0.01). CypD-deficient mice displayed an increased expression of ER stress proteins such as eukaryotic initiation factor 2α (eIF2α) or glucose regulated protein 78 (Grp78 or Bip). The ER stress inhibitor TUDCA prevented the infarct size reduction afforded by the loss of cypD function (mean infarct size averaged 21 ± 4% of LV weight, p < 0.01 vs. cypD-KO). Similar results were obtained when NIM811, an analog of cyclosporine A, was used to pharmacologically (instead of genetically) inhibit cypD function. This study suggests that the ER stress induced by the inhibition of cypD function plays a key role in protecting the heart against lethal ischemia-reperfusion injury.
MeSH term(s)	Animals ; Peptidyl-Prolyl Isomerase F ; Cyclophilins/antagonists & inhibitors ; Cyclophilins/deficiency ; Cyclophilins/genetics ; Cyclophilins/metabolism ; Cyclosporine/pharmacology ; Cyclosporins/pharmacology ; Disease Models, Animal ; Endoplasmic Reticulum Chaperone BiP ; Endoplasmic Reticulum Stress/drug effects ; Endoplasmic Reticulum Stress/physiology ; Heart/drug effects ; Heart/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondrial Membranes/metabolism ; Myocardial Infarction/pathology ; Myocardial Infarction/physiopathology ; Myocardial Infarction/prevention & control ; Myocardial Reperfusion Injury/physiopathology ; Myocardial Reperfusion Injury/prevention & control ; Taurochenodeoxycholic Acid/pharmacology
Chemical Substances	Peptidyl-Prolyl Isomerase F ; Cyclosporins ; Endoplasmic Reticulum Chaperone BiP ; Hspa5 protein, mouse ; PPIF protein, mouse ; Taurochenodeoxycholic Acid (516-35-8) ; ursodoxicoltaurine (60EUX8MN5X) ; Cyclosporine (83HN0GTJ6D) ; (melle-4)cyclosporin (96262S4I14) ; Cyclophilins (EC 5.2.1.-)
Language	English
Publishing date	2013-06-07
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	189755-x
ISSN	1435-1803 ; 0300-8428 ; 0175-9418
ISSN (online)	1435-1803
ISSN	0300-8428 ; 0175-9418
DOI	10.1007/s00395-013-0363-z
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Article ; Online: Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles.

Rabia, Maxence / Leuzy, Valentin / Soulage, Christophe / Durand, Annie / Fourmaux, Baptiste / Errazuriz-Cerda, Elisabeth / Köffel, René / Draeger, Annette / Colosetti, Pascal / Jalabert, Audrey / Di Filippo, Mathilde / Villard-Garon, Audrey / Bergerot, Cyrille / Luquain-Costaz, Céline / Moulin, Philippe / Rome, Sophie / Delton, Isabelle / Hullin-Matsuda, Françoise

Biochimie

2020 Volume 178, Page(s) 26–38

Abstract: Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in ... ...

Abstract	Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible biomarker of disorders such as genetic lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific lipid in biofluids. The present study demonstrates that in absence of any sign of renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary biomarker of amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new lipid marker of urinary exosomes.
MeSH term(s)	Aged ; Amiodarone/adverse effects ; Animals ; Anti-Arrhythmia Agents/adverse effects ; Biomarkers/urine ; Endosomes/chemistry ; Endosomes/drug effects ; Endosomes/metabolism ; Extracellular Vesicles/chemistry ; Extracellular Vesicles/drug effects ; Extracellular Vesicles/metabolism ; Female ; HEK293 Cells ; Humans ; Kidney Diseases/chemically induced ; Lysophospholipids/chemistry ; Lysophospholipids/metabolism ; Lysosomes/drug effects ; Lysosomes/metabolism ; Macrophages/chemistry ; Macrophages/drug effects ; Macrophages/metabolism ; Male ; Middle Aged ; Monoglycerides/chemistry ; Monoglycerides/metabolism ; Pilot Projects ; Rats ; THP-1 Cells
Chemical Substances	Anti-Arrhythmia Agents ; Biomarkers ; Lysophospholipids ; Monoglycerides ; bis(monoacylglyceryl)phosphate ; Amiodarone (N3RQ532IUT)
Language	English
Publishing date	2020-07-10
Publishing country	France
Document type	Journal Article
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2020.07.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Uc I Zs.135: Show issues

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