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Vitamin D modulates the content of inflammatory microRNAs in extracellular vesicles from human adipocyte cells in inflammatory context

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BIOFACTORS 2025年第1期51卷 e70003页

作者： payet, thomas Astier, Julien Bournot, Lorrine Sicard, Flavie Robert, Stephane Lacroix, Romaric Wabitsch, Martin Landrier, Jean-Francois Mounien, Lourdes Aix Marseille Univ INSERM INRAE C2VN Marseille France Biomeostasis CRO Nutr Behav & Metab Disorders La Penne Sur Huveaune France PhenoMARS Aix Marseille Technol Platform CriBiom Marseille France Biogenopole Dept Haematol CHU Timone AP HM Marseille France Ulm Univ Med Ctr Dept Pediat & Adolescent Med Ulm Germany

Inflammation of adipose tissue is a contributing factor to many chronic diseases associated with obesity. We previously showed that micronutrients such as vitamin D (VD) limited this metabolic inflammation by decreasing inflammatory markers expression including miR-155 (microRNA-155) or miR-146a in different in vitro and in vivo models. These miRNAs could be incorporated into extracellular vesicles (EVs) in order to modulate the activity of target cells. Nevertheless, the role of VD on the miRNAs contained in EVs from adipose tissue in inflammatory conditions remains unclear. In this study, we used a human model of SGBS (Simpson-Golabi-Behmel syndrome) adipocytes preincubated with 1,25(OH)2D (the active form of VD) before an inflammatory stress with tumor necrosis factor alpha (TNF alpha). First, we confirmed by quantitative PCR that the expression of classical inflammatory factors (TNF alpha and chemokine ligand 2 [CCL2/MCP1]), miR-146a, and miR-155 was increased significantly under inflammatory conditions in SGBS cells and that VD prevented this up-regulation. Secondly, transmission electron microscope imaging of EVs preparations in supernatant allowed visualization of small and large vesicles under these conditions. Then, EVs were obtained with isolation kit and the expression of miR-155 and miR-146a were measured. The expression of miR-155 under TNF alpha effect was increased in EVs while miR-146a was not detected. Moreover, we also showed that the TNF alpha-mediated expression of miR-155 in EVs was significantly reduced by a VD pre-incubation of cells. Using miRNA PCR array, we also identified 33 miRNAs, organized in 5 clusters that were differentially regulated by TNF alpha and VD. Bioinformatic analysis of biological pathways revealed that the different miRNAs targeting genes that are involved in important cell process such as the regulation of transcription or protein phosphorylation. In conclusion, these results support for the first time that VD modulated

关键词： Vitamin D extracellular vesicles inflammation human adipocyte microRNAs

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Vitamin D metabolism is altered during aging alone or combined with obesity in male mice

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BIOFACTORS 2024年第5期50卷 957-966页

作者： Bournot, Lorrine payet, thomas Marcotorchino, Julie Awada, Manar Rouquet, Thais Breniere, thomas Couturier, Charlene Astier, Julien Halimi, Charlotte Reboul, Emmanuelle Sicard, Flavie Mounien, Lourdes Roux, Julien Bariohay, Bruno Landrier, Jean Francois Aix Marseille Univ INSERM INRAE C2VN Marseille France Biomeostasis La Penne Sur Huveaune France CriBiom PhenoMARS Marseille France Aix Marseille Univ INSERM 1263 UMR 1260 INRAE 27 Bd Jean Moulin F-13385 Marseille 05 France Aix Marseille Univ C2VN 27 Bd Jean Moulin F-13385 Marseille 05 France

Aging and obesity are associated with a decrease in plasma 25-hydroxyvitamin D (25(OH)D) levels. In the context of a growing aging population and the rising incidence of obesity, we hypothesized that aging process, either independently or in combination with obesity, could influence vitamin D (VD) metabolism, consequently resulting in the reduced 25(OH)D plasma concentrations. C57BL/6JRJ young (6 months) and old (23 months) mice fed with control (CD) or high fat diet (HF) were compared. Plasma and adipose concentration of cholecalciferol and 25(OH)D and mRNA expression of genes coding for the main VD actors were analyzed. Aging was associated with a decrease in plasma 25(OH)D levels, whereas combined effect of obesity and aging did not generate a cumulative effect on plasma 25(OH)D levels. The mRNA expression of Cyp27a1, Cyp3a11, and Cyp2j6 were decreased in the liver during aging. Together, these regulations could explain the reduced 25-hydroxylation. Interestingly, the lack of cumulative reduction of 25(OH)D in aged and obese mice could be related to the strong induction of Cyp2j6. In kidneys, a complex modulation of Cyp27b1 and Cyp24a1 could contribute to the reduced 25-hydroxylation in the liver. In white adipose tissue, an induction of Cyp2r1 was observed during aging and obesity, together with an increase of 25(OH)D quantity, suggesting an exacerbated storage that may participated to the reduced plasma 25(OH)D levels. These findings support the notion that aging alone or combined with obesity, induces regulation of VD metabolism in the organs, beyond the classical reduction of epidermal VD precursor, which may contribute to the decrease in 25(OH)D levels. We report for the first time the effect of aging process alone or in combination with obesity on vitamin D metabolism as a whole and leading to modulation of 25(OH)D plasma levels. Our data strongly suggest that the enzymes involved in vitamin D metabolism, notably in liver, kidneys, and adipose tissue, are t

关键词： aging kidneys liver obesity vitamin D white adipose tissue

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Role of micro-RNAs associated with adipose-derived extracellular vesicles in metabolic disorders

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OBESITY REVIEWS 2024年第7期25卷 e13755-e13755页

作者： payet, thomas Gabinaud, Elisa Landrier, Jean-Francois Mounien, Lourdes Aix Marseille Univ INRAE INSERM C2VN Marseille France PhenoMARS Aix Marseille Technol Platform CriBiom Marseille France Univ Aix Marseille INSERM UMR 1260 INRA 1062 27 Bd Jean Moulin F-13385 Marseille France

Micro-RNAs have emerged as important actors in the onset of metabolic disorders including obesity or type 2 diabetes. Particularly, several micro-RNAs are known to be key modulators of lipid metabolism, glucose homeostasis, or feeding behavior. Interestingly, the role of extracellular vesicles containing micro-RNAs, especially adipose-derived extracellular vesicles, are well-documented endocrine signals and disease biomarkers. However, the role of adipose-derived extracellular vesicles on the different tissues is different and highly related to the micro-RNA content. This review provides recent data about the potential involvement of adipose-derived extracellular vesicle-containing micro-RNAs in metabolic diseases.

关键词： adipose tissue extracellular vesicles metabolic syndrome micro-RNAs

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Aging alone or combined with obesity increases white adipose tissue inflammatory status in male mice

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SCIENTIFIC REPORTS 2024年第1期14卷 1-10页

作者： Bournot, Lorrine payet, thomas Sicard, Flavie Breniere, thomas Astier, Julien Roux, Julien Bariohay, Bruno Landrier, Jean-Francois Aix Marseille Univ INRAE INSERM C2VN F-13000 Marseille France Biomeostasis F-13070 La Penne Sur Huveaune France CriBiom PhenoMARS Marseille France Aix Marseille Univ C2VN INSERM INRAE 1263UMR 1260 27 Bd Jean Moulin F-13385 Marseille 5 France

White adipose tissue (WAT) has been recognized as a fundamental and crucial organ of interest in research focusing on inflammation during obesity or aging. WAT is also proposed as a significant component of cholecalciferol and 25-hydroxyvitamin D (25(OH)D) storage, which participates in the decrease of 25(OH)D plasma levels reported during aging and obesity. In the present study, we evaluated WAT and plasma cholecalciferol and 25(OH)D content together with inflammatory status to highlight the putative relationship between vitamin D status and inflammatory process during aging alone or combined with obesity. Circulating cholecalciferol and 25(OH)D and the stored quantity of cholecalciferol and 25(OH)D in WAT were quantified in young and old mice fed a control or obesogenic diet. The inflammation was assessed by measuring plasma inflammatory cytokines, mRNA, and microRNAs inflammatory-associated in WAT. The combination of aging and obesity decreased 25(OH)D plasma levels but did not modify circulating inflammatory markers. A cumulative effect of aging and obesity was observed in WAT, with rising mRNA inflammatory cytokines, notably Ccl5 and Tnf. Interestingly, aging and obesity-associated were also characterized by increased inflammatory microRNA expression. The inflammatory parameters in WAT were negatively correlated with the plasma 25(OH)D but positively correlated with the quantity of cholecalciferol and 25(OH)D in WAT. These results support the cumulative effect of obesity and aging in aggravation of WAT inflammation and suggest that accumulation of cholecalciferol and 25(OH)D in WAT could constitute a mechanism to counteract WAT inflammation during aging and obesity.

关键词： Inflammatory Vitamin D Aging Obesity Mice Adipose tissue

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Proposal of a bioinformatics approach to predict molecular mechanisms involved in inflammatory response: case of ATRA and 1,25(OH)2D in adipocytes

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EPIGENETICS 2023年第1期18卷

作者： Karkeni, Esma payet, thomas Astier, Julien Sicard, Flavie Mounien, Lourdes Landrier, Jean-Francois Aix Marseille Univ INRAE INSERM C2VN Marseille France INSERM INRAE PhenoMars CriBiomC2VN Marseille France Univ Aix Marseille INSERM INRA 1062 UMR 1260 27 Bd Jean Moulin F-13385 Marseille 05 France

Several inflammatory markers such as cytokines, chemokines, and microRNAs (miRNAs) are well known to be induced during obesity and are strongly linked to their comorbidities. Among many others factors, the micronutrient status is suspected to reduce obesity-associated inflammation via blunting inflammatory signalling pathways. This is notably the case for active forms of vitamin A (all-trans retinoic acid ATRA) and vitamin D (1,25(OH)(2)D) as previously shown. In the present study, we aimed to implement a new bioinformatics approach to unveil commonly regulated signalling pathways through a combination of gene and miRNA expression sets impacted by ATRA and 1,25(OH)(2)D in adipocytes. In a first set of experiments, we focused only our attention on ATRA and demonstrated that it reduced LPS-mediated miRNA expression (miR-146a, miR-150, and miR-155) in mouse adipose tissue, in adipocyte cultures, and in adipocyte-derived vesicles. This result was confirmed in TNFa-induced miRNA in human adipocytes. Then, bioinformatic analysis highlighted that both ATRA and 1,25(OH)(2)D-regulated genes and miRNA converge to the canonical 'nuclear factor Kappa B (NF-?B) signalling pathway.' Altogether, these results showed that ATRA has anti-inflammatory effects on miRNA expression. In addition, the proposed bioinformatic model converges to NF-?B signalling pathway that has been previously demonstrated to be regulated by ATRA and 1,25(OH)(2)D, thus confirming the interest of such approach.

关键词： NF-kappa B bioinformatics adipocytes adipose tissue vitamins vitamin a vitamin D

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Vitamin D Modulates Lipid Composition of Adipocyte-Derived Extracellular Vesicles Under Inflammatory Conditions

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MOLECULAR NUTRITION & FOOD RESEARCH 2023年第22期67卷 2300374-2300374页

作者： payet, thomas Valmori, Marie Astier, Julien Svilar, Ljubica Sicard, Flavie Tardivel, Catherine Ghossoub, Rania Martin, Jean-Charles Landrier, Jean-Francois Mounien, Lourdes Aix Marseille Univ INSERM INRAE C2VN Marseille France BIOMET Marseille France PhenoMARS Aix Marseille Technol Platform Marseille France Aix Marseille Univ Inst Paoli Calmettes Ctr Rech Cancerol Marseille CRCM Equipe Labellisee Ligue 2018INSERMCNRS Marseille France

Scope: Adipocyte-derived extracellular vesicles (AdEVs) convey lipids that can play a role in the energy homeostasis. Vitamin D (VD) has been shown to limit the metabolic inflammation as it decreases inflammatory markers expression in adipose tissue (AT). However, VD effect on adipocytes-derived EVs has never been *** and results: Thus, the aim of this study is to evaluate the AdEVs lipid composition by LC-MS/MS approach in 3T3-L1 cells treated with VD or/and pro-inflammatory factor (tumor necrosis factor alpha [TNF alpha]). Among all lipid species, four are highlighted (glycerolipids, phospholipids, lysophospholipids, and sphingolipids) with a differential content between small (sEVs) and large EVs (lEVs). This study also observes that VD alone modulates EV lipid species involved in membrane fluidity and in the budding of membrane. EVs treated with VD under inflammatory conditions have different lipid profiles than the control group, which is more pronounced in lEVs. Indeed, 25 lipid species are significantly modulated in lEVs, compared with only seven lipid species in ***: This study concludes that VD, alone or under inflammatory conditions, is associated with specific lipidomic signature of sEVs and lEVs. These observations reinforce current knowledge on the anti-inflammatory effect of VD. The adipocyte-derived extracellular vesicles convey lipids that could play a role in the energy homeostasis. It has been shown that vitamin D limit the metabolic inflammation by decreasing inflammatory markers expression in adipose tissue. This study demonstrated that vitamin D alone or in inflammatory condition induced by TNF alpha are associated with specific lipid signature of small and large extracellular vesicles from adipocyte. The current study provided a new perspective in the anti-inflammatory action of vitamin ***

关键词： adipocyte extracellular vesicles inflammation lipidomic obesity vitamin D

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Nonuniform mobility-enhancement techniques and their impact on device performance

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IEEE TRANSACTIONS ON ELECTRON DEVICES 2008年第4期55卷 1050-1057页

作者： payet, Fabrice Boeuf, Frederic Ortolland, Claude Skotnicki, thomas STMicroelect F-38920 Crolles France NXP Semicond F-38926 Crolles France

Nowadays, process-induced stress is the preferential industrial method to enhance circuit performances. One of the most popular techniques is the strain induced by contact etch-stop layer. This technology induces a drain-current enhancement which depends on the device dimensions. This strong behavior has already been reported in the literature. In this paper, we propose a simple semianalytical physical model to understand the origin of this dependence and to highlight the physical limitations of the stress techniques. With this model, after a calibration, it would be possible to predict the MOSFET performance for a given transistor gate length. This approach is validated by experimental data and explains the reduction of the drain-current enhancement that is observed for ultrasmall gate-length MOSFET.

关键词： contact etch-stop layer (CESL) mobility mobility enhancement MOSFETs SiN liner strained Si

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Development of an electro-thermal resistive switching model based on O-Frenkel pairs to study reset and set mechanisms in HfO2-based RRAM cells

Development of an electro-thermal resistive switching model ...

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International Conference on Simulation of Semiconductor Processes and Devices (SISPAD)

作者： Cueto, Olga payet, Anthony Cabout, thomas Univ Grenoble Alpes CEA LETI F-38054 Grenoble France

ISBN: (纸本)9781479952885

An electro-thermal resistive switching model based on O-Frenkel pairs is presented. This model relies on partial differential equations and is used to simulate reset and set mechanisms for HfO2-based RRAM devices starting from an existing conductive filament. First simulations indicate that the model can fairly reproduce experimental ON and OFF resistances.

关键词： oxide based RRAM simulation switching model O-Frenkel pairs

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Structural requirements for cooperative binding of HMG1 to DNA minicircles

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JOURNAL OF MOLECULAR BIOLOGY 2001年第1期309卷 79-88页

作者： Webb, M payet, D Lee, KB Travers, AA thomas, JO Univ Cambridge Cambridge Ctr Mol Recognit Cambridge CB2 1GA England Univ Cambridge Dept Biochem Cambridge CB2 1GA England MRC Mol Biol Lab Cambridge CB2 2QH England

DNA minicircles, where the length of DNA is below the persistence length, are highly effective, preferred, ligands for HMG-box proteins. The proteins bind to them "structure-specifically" with affinities in the nanomolar range, presumably to an exposed widened minor groove. To understand better the basis of this preference, we have studied the binding of HMG1 (which has two tandem HMG boxes linked by a basic extension to a long acidic tail) and Drosophila HMG-D tone HMG box linked by a basic region to a short and less acidic tail), and their HMG-box domains, to 88 bp and 75 bp DNA minicircles. In some cases we see cooperative binding of two molecules to the circles. The requirements for strong cooperativity are two HMG boxes and the basic extension;the latter also appears to stabilize and constrain the complex, preventing binding of further protein molecules. HMG-D, with a single HMG box, does not bind cooperatively. Ln the case of HMG1, the acidic tail is not required for cooperativity and does not affect binding significantly, in contrast to a much greater effect with linear DNA, or even four-way junctions (another distorted DNA substrate). Such effects could be relevant in the hierarchy of binding of HMG-box proteins to DNA distortions in vivo, where both single-box and two-box proteins might co-exist, with or without basic extensions and acidic tails. (C) 2001 Academic Press.

关键词： HMG-box DNA minicircles DNA bending cooperativity

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Integrating conservation, restoration and land-use planning in islands-An illustrative case study in Reunion Island (Western Indian Ocean)

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LANDSCAPE AND URBAN PLANNING 2011年第2期101卷 120-130页

作者： Lagabrielle, Erwann Rouget, Mathieu Le Bourgeois, thomas payet, Karine Durieux, Laurent Baret, Stephane Dupont, Joel Strasberg, Dominique Nelson Mandela Metropolitan Univ ZA-6530 George South Africa IRD Reunion IRD UMR ESPACE DEV 128 F-97492 St Clothilde France Univ Reunion CIRAD UMR PVBMT F-97410 St Pierre France S African Natl Biodivers Inst ZA-0001 Pretoria South Africa Univ Pretoria Dept Plant Sci ZA-0002 Pretoria South Africa Univ Stellenbosch Dept Conservat Ecol & Entomol ZA-7602 Matieland South Africa IRD Bresil IRD UMR ESPACE DEV 128 BR-71619970 Brasilia DF Brazil Parc Natl La Reunion F-97400 St Denis France Soc Reunionnaise Etud & Protect Environm F-97490 St Clothilde France CIRAD UMR AMAP F-34730 Montpellier 5 France

This paper describes an operational protocol for integrating conservation and restoration with land-use planning in islands. Conservation challenges are intensified in insular systems due to higher ecosystem vulnerability, limited spatial options, low data availability, rapid land-use change and, globally, short-term vision planning. Our operational planning protocol integrates ecological and socio-economic factors to identify the best spatial options for conserving and restoring biodiversity, inside and outside extant reserves, while minimising future land-use conflicts. Conservation and restoration targets are formulated for species, habitats and ecological processes that support biodiversity. An optimal network of priority sites is selected to achieve those targets across the landscape. The prioritisation process integrates a Conservation Costs Index to optimise conservation and restoration investments. We discuss the outcomes of the planning protocol in terms of site prioritisation, stakeholders' participation and general implications for spatial planning in insular systems. As with many islands, the study area of Reunion Island has experienced rapid urban and agricultural expansion, which threatens its unique biodiversity. Forty three per cent of the island is currently protected in a National Park but only half of this reserve network contributes to the achievement of targets. An additional 21% of land should be conserved mainly to ensure the persistence of ecological connections between the marine, terrestrial and freshwater realms. Finally we emphasize that our method doesn't substitute the land-use planning debate but is aimed to better prepare the conservation sector for negotiating future land-use allocation with other socio-economic sectors in islands. (C) 2011 Elsevier B.V. All rights reserved.

关键词： Biodiversity GIS Cost optimisation Corridors Protected areas Invasion

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