Effect of apoA-I on cholesterol release and apoE secretion in human mature adipocytes

<p>Abstract</p> <p>Background</p> <p>The risk of cardiovascular disease is inversely correlated to level of plasma HDL-c. Moreover, reverse cholesterol transport (RCT) from peripheral tissues to the liver is the most widely accepted mechanism linked to the anti-atherosclerotic activity of HDL. The apolipoprotein A-I (apoA-I) and the ABC transporters play a key role in this process.</p> <p>Adipose tissue constitutes the body's largest pool of free cholesterol. The adipose cell could therefore be regarded as a key factor in cholesterol homeostasis. The present study investigates the capacity of primary cultures of mature human adipocytes to release cholesterol and explores the relationships between apoA-I, ABCA1, and apoE as well as the signaling pathways that could be potentially involved.</p> <p>Results</p> <p>We demonstrate that apoA-I induces a strong increase in cholesterol release and apoE secretion from adipocytes, whereas it has no transcriptional effect on ABCA1 or apoE genes. Furthermore, brefeldin A (BFA), an intracellular trafficking inhibitor, reduces basal cholesterol and apoE secretion, but does not modify induction by apoA-I. The use of statins also demonstrates that apoA-I stimulated cholesterol release is independent of HMG-CoA reductase activation.</p> <p>Conclusion</p> <p>Our work highlights the fact that adipose tissue, and particularly adipocytes, may largely contribute to RCT <it>via </it>a mechanism specifically regulated within these cells. This further supports the argument that adipose tissue must be regarded as a major factor in the development of cardiovascular diseases, in particular atherosclerosis.</p

L’adipocyte au coeur de la physiopathologie Obésité / Diabète. Petit voyage moléculaire et cellulaire dans le tissu adipeux

Global incidence of obesity has increased dramatically during the last decades. The situation has become particularly alarming since obesity epidemic started to spread among children. Consequently, the impact of adipose tissue development on health, especially in excess fat accumulation conditions like obesity, has been highly studied. Adipose tissue function is critical for whole body homeostasis ; this endocrine organ controls energy metabolism, modulates lipid flux, and secretes factors exhibiting endocrine, paracrine and autocrine activities. The dysregulation of adipocyte functions caused by chronic excess of energy has been directly involved in the etiology of metabolic disorders such as insulin resistance, type 2 diabetes and cardiovascular diseases. In view of the above considerations, this study was performed to detail the importance of fat mass in the body homeostasis. The study allowed the identification of new regulators of adipocyte functions and brings new evidence of adipocyte involvement in metabolic disorders.Au cours de l’évolution des hominidés, le stockage d’énergie sous forme de masse grasse a constituté un chaînon essentiel à la survie des espèces. Cependant, durant les derniers millénaires, la mécanisation de la vie et la généralisation de comportements alimentaires inadaptés ont créé un environnement propice à l’apparition de l’obésité, devenue épidémie mondiale depuis la fin du XXème siècle. Le stockage de l’excédent énergétique sous la forme de masse grasse dans le tissu adipeux est une réponse métabolique adaptée à l’environnement moderne. Cependant, avec un seuil propre à chaque individu, l’excès énergétique finit par créer un état de stress dans le tissu adipeux, conduisant à la dérégulation des fonctions de stockage et de sécrétion des cellules adipocytaires. Les adipocytes sécrètent en effet une myriade de facteurs agissant sur des fonctions essentielles telles que l’immunité, la reproduction, le comportement alimentaire, la prolifération et la mortalité cellulaire. La dérégulation des fonctions adipocytaires conséquente à des excès alimentaires chroniques est directement à l’origined’importantes pathologies métaboliques comme l’insulino-resistance, le diabète de type 2 et les maladies cardiovasculaires. Le tissu adipeux est donc un régulateur prédominant de l’équilibre corporel. Au cours de cette étude, je me suis intéressée à détailler l’importance de la masse grasse à l’échelle de l’organisme, et j’ai identifié de nouveaux éléments régulateurs du fonctionnement des cellules adipocytaires. Ce travail apporte de nouvelles données sur l’implication du tissu adipeux dans les maladies associées à l’obésité

La Reunion dans l'ERA : Feuille de route pour l'intégration de La Réunion dans l'Espace Européen de la Recherche et de l'Innovation

&lt;p&gt;La présente feuille de route rassemble des actions conçues pour d'améliorer l'intégration de La Réunion dans l'Espace Européen de la Recherche et de l'Innovation (ERA) et sa participation aux programmes-cadres pour la Recherche et l'Innovation (Horizon 2020 / Horizon Europe). Elle a été élaborée par Nexa, l'agence de Développement et d'Innovation de La Réunion, à partir des travaux menés dans le cadre de la stratégie régionale de spécialisation intelligente (S3) de La Réunion, du projet Horizon 2020-FORWARD sur la R&amp;I dans les RUP (Grant agreement n° 824550) avec l'appui de la communauté de la recherche et de l'innovation de La Réunion.&lt;/p&gt;&lt;p&gt;This roadmap brings together actions designed to improve the integration of La Reunion into the European Research and Innovation Area (ERA) and its participation in the Framework programmes for Research and Innovation (Horizon 2020 / Horizon Europe). It was developed by Nexa, the regional agency for Development &amp; Innovation of La Reunion, based on work carried out as part of the regional smart specialization strategy (S3) of La Reunion, as well as of the Horizon 2020-FORWARD project (Grant agreement no. 824550) with the support of the community of research and innovation in La Réunion.&lt;/p&gt

Ile en transitions : plan d'action pour la Recherche et l'Innovation à La Réunion (2021-2027)

&lt;p&gt;Ce document présente un état des lieux de l'économie de la connaissance à La Réunion, un diagnostic du système de recherche et d'innovation ainsi que des propositions d'interventions pour accélérer la transformation de La Réunion.&lt;/p&gt;&lt;p&gt;This document presents a state-of-play of the knowledge economy in La Reunion, a diagnosis of the research and innovation system as well as priority actions to accelerate the transformation of La Reunion.&lt;/p&gt

La Reunion, a European living lab in the Indian Ocean. Research and innovation projects funded by the European Union.

This document presents the Research and innovation projects funded by the European Union of La Reunion, from 2024 to 2020. This book serves as inspirational material to showcase the benefits of EU collaborative projects for La Reunion's stakeholders. It also gives EU stakeholders a positive perception of La Reunion as a relevant partner for R&I project

Opinion: What is the scale on my histological drawings? A blood tip at la Reunion Island University

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Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase.: Secretion and Activity of Adipocyte Autotaxin

Autotaxin (ATX) is a lysophospholipase D involved in synthesis of lysophosphatidic acid (LPA). ATX is secreted by adipocytes and is associated with adipogenesis and obesity-associated diabetes. Here we have studied the mechanisms involved in biosynthesis and secretion of ATX by mouse 3T3-F442A adipocytes. We found that inhibition of N-glycosylation with tunicamycin or by double point deletion of the amino-acids N53 and N410 of ATX inhibit its secretion. In addition, N-glycosidase treatment and point deletion of the amino-acid N410 inhibits the lysophospholipase D activity of ATX. Analysis of the amino-acid sequence of mouse ATX shows the presence of a N-terminal signal peptide. Treatment with the signal peptidase inhibitor globomycin inhibits ATX secretion by adipocytes. Transfection in Cos-7 cells of site-directed deleted ATX shows that ATX secretion is dependent on the hydrophobic core sequence of the signal peptide, not on the putative signal peptidase cleavage site sequence. Analysis of the amino-acid sequence of mouse ATX also reveals the presence of a putative cleavage site by the protein convertase furin. Treatment of adipocytes with the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone does not modified secretion or lysophospholipase D activity of ATX. Transfection in Cos-7 cells of site-directed deleted ATX shows that the furin recognition site is not required for secretion or lysophospholipase D activity of ATX. In conclusion, the present work demonstrates the crucial role of N-glycosylation in secretion and activity of ATX. The present work also confirms the crucial role signal peptidase in secretion of ATX by adipocytes