Origines, rôles et conséquences de l'inflammation du tissu adipeux chez le sujet obèse (de nouvelles hypothèses)

Au cours de l obésité, le tissu adipeux (TA) est caractérisé par une inflammation chronique de faible intensité dont les médiateurs cellulaires, moléculaires et les conséquences sur le tissu ne sont pas entièrement définis. En particulier, l inflammation du TA est associée à un remodelage important de sa matrice extracellulaire pouvant aboutir à l apparition de fibrose. L étude de la fibrose du TA humain nous a permis de mettre en évidence la présence de collagènes de type I, III et VI disposés en amas, en travées entre les lobules adipocytaires et autour de chaque vaisseaux. Chez le sujet obèse, nous avons observé une augmentation de la fibrose autour des adipocytes. Sa quantité dans le TA sous-cutané influence les variations de masse grasse au cours de l amaigrissement induit par la chirurgie bariatrique. Ces zones de fibrose fortement vascularisées contiennent des macrophages, des cellules fibroblastiques et des mastocytes dont le nombre est positivement corrélé à la surface de fibrose mesurée. Les mastocytes semblent être un acteur important de la mise en place de l obésité. Nous avons en effet montré que des souris sans mastocyte résistent à la prise de poids. Afin de déterminer leur rôle dans l obésité humaine, nous avons identifié, isolé et caractérisé les mastocytes du TA. Leur profil sécrétoire, fortement inflammatoire chez l obèse, ainsi que leur action sur les cellules endothéliales, suggèrent leur implication dans l inflammation du TA. En résumé, notre travail a contribué à montrer l importance des altérations pathologiques du TA au cours de l obésité humaine au travers la contribution des mastocytes dans les phénomènes immuno-inflammatoires et fibrotiques.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

« L’enseignement technique rural au féminin. L’exemple de quelques écoles ménagères agricoles privées du Doubs (années 1900-années 1960) »

International audienc

Entre morale, enseignement technique et tâches ménagères : les écoles ménagères agricoles publiques du Doubs (1910- 1960)

Les écoles ménagères agricoles proposent des enseignements techniques destinés aux jeunes filles vivant à la campagne. Il s’agit de les convaincre de travailler au sein de la ferme familiale dans leur village, dans un contexte où, sur la période1910-1960, l’exode rural est élevé. Nous mobilisons l’étude de cas du département du Doubs, où tous les types d’écoles ménagères coexistent durant la période étudiée. Nous montrons l’importance des enseignements ménagers agricoles pour les jeunes rurales. S’ils ne sont guère un facteur d’émancipation féminine radical, ils n’en occupent pas moins une place, aussi modeste soit-elle, dans les évolutions du rôle des femmes en milieu rural, durant la première moitié du XXe, qui leur permet de s’affranchir, en partie, de certains carcans de la domination masculine.Technical teaching within agricultural home economics schools was specifically proposed to young women coming from the countryside. The aim was to convince these women to work in their village family farm, in a period when rural-urban migration increased (1910-1960). During this period, in the Doubs region, all types of home economics schools were coexisting. Our contention is to show how important this agricultural household teaching was for these young rural women. Although this teaching did not allow them to be radically emancipated, it humbly enabled them to evolve in rural areas during the first half of the 20th century. This represented a way to achieve independence and be freed from some constraints imposed by the patriarchal society.In landwirtschaftlichen Hauswirtschaftsschulen erhielten junge Mädchen auf dem Lande eine fachliche Ausbildung. Ziel war es, sie zu überzeugen, auf dem Hof der Familie in ihrem Dorf zu arbeiten. Hintergrund war die hohe Landflucht in den Jahren zwischen 1910 und 1960. Wir untersuchen den Fall des Departements Doubs, wo im untersuchten Zeitraum alle Arten von Hauswirtschaftsschulen nebeneinander existierten. Wir zeigen die Bedeutung des Unterrichtens der Haus- und Landwirtschaft für die Landjugend. Obwohl diese Lehre wohl kaum ein einschneidender Faktor in der Frauenemanzipation gewesen ist, nimmt sie dennoch einen – wenn auch bescheidenen – Platz in der Entwicklung der Rolle der Frau auf dem Lande in der ersten Hälfte des 20. Jahrhunderts ein, da sie es den Frauen ermöglichte, sich zumindst von einigen Fesseln der männlichen Vorherrschaft zu befreien.Las escuelas domésticas agrícolas proponen enseñanza técnica para las jóvenes que viven en el campo. La idea es convencerlas de trabajar en la finca familiar de su pueblo, en un contexto, durante el período 1910-1960, de éxodo rural alto. Utilizamos el estudio de caso del departamento de Doubs, donde coexistieron todo tipo de escuelas domésticas durante el período estudiado. Mostramos la importancia de la enseñanza doméstica agrícola para las jóvenes rurales. Si bien no son un factor de emancipación femenina radical, sin embargo ocupan un lugar, por modesto que sea, en la evolución del papel de la mujer en el medio rural durante la primera mitad del siglo XX, que le permitió liberarse, en parte, de ciertos yugos de la dominación masculina

Entre morale, enseignement technique et tâches ménagères : les écoles ménagères agricoles publiques du Doubs (1910- 1960)

International audienceLes écoles ménagères agricoles proposent des enseignements techniques destinés aux jeunes filles vivant à la campagne. Il s’agit de les convaincre de travailler au sein de la ferme familiale dans leur village, dans un contexte où, sur la période1910-1960, l’exode rural est élevé. Nous mobilisons l’étude de cas du département du Doubs, où tous les types d’écoles ménagères coexistent durant la période étudiée. Nous montrons l’importance des enseignements ménagers agricoles pour les jeunes rurales. S’ils ne sont guère un facteur d’émancipation féminine radical, ils n’en occupent pas moins une place, aussi modeste soit-elle, dans les évolutions du rôle des femmes en milieu rural, durant la première moitié du XXe, qui leur permet de s’affranchir, en partie, de certains carcans de la domination masculine

Differential Open Chromatin Profile And Transcriptomic Signature Define Depot-Specific Human Subcutaneous Preadipocytes: Primary Outcomes

Background: Increased lower body fat is associated with reduced cardiometabolic risk. The molecular basis for depot-specific differences in gluteofemoral (GF) compared with abdominal (A) subcutaneous adipocyte function is poorly understood. In the current report, we used a combination of Assay for Transposase-Accessible Chromatin followed by sequencing (ATAC-seq), RNA-seq, and chromatin immunoprecipitation (ChIP)-qPCR analyses that provide evidence that depot-specific gene expression patterns are associated with differential epigenetic chromatin signatures. Methods: Preadipocytes cultured from A and GF adipose tissue obtained from premenopausal apple-shaped women were used to perform transcriptome analysis by RNA-seq and assess accessible chromatin regions by ATAC-seq. We measured mRNA expression and performed ChIP-qPCR experiments for histone modifications of active (H3K4me3) and repressed chromatin (H3K27me3) regions respectively on the promoter regions of differentially expressed genes. Results: RNA-seq experiments revealed an A-fat and GF-fat selective gene expression signature, with 126 genes upregulated in abdominal preadipocytes and 90 genes upregulated in GF cells. ATAC-seq identified almost 10-times more A-specific chromatin-accessible regions. Using a combined analysis of ATAC-seq and global gene expression data, we identified 74 of the 126 abdominal-specific genes (59%) with A-specific accessible chromatin sites within 200 kb of the transcription start site (TSS), including HOXA3, HOXA5, IL8, IL1b, and IL6. Interestingly, only 14 of the 90 GF-specific genes (15%) had GF-specific accessible chromatin sites within 200 kb of the corresponding TSS, including HOXC13 and HOTAIR, whereas 25 of them (28%) had abdominal-specific accessible chromatin sites. ChIP-qPCR experiments confirmed that the active H3K4me3 chromatin mark was significantly enriched at the promoter regions of HOXA5 and HOXA3 genes in abdominal preadipocytes, while H3K27me3 was less abundant relative to chromatin from GF. This is consistent with their A-fat specific gene expression pattern. Conversely, analysis of the promoter regions of the GF specific HOTAIR and HOXC13 genes exhibited high H3K4me3 and low H3K27me3 levels in GF chromatin compared to A chromatin. Conclusions: Global transcriptome and open chromatin analyses of depot-specific preadipocytes identified their gene expression signature and differential open chromatin profile. Interestingly, A-fat-specific open chromatin regions can be observed in the proximity of GF-fat genes, but not vice versa. Trial registration: Clinicaltrials.gov, NCT01745471. Registered 5 December 2012

Transcriptional and DNA Methylation Signatures of Subcutaneous Adipose Tissue and Adipose-Derived Stem Cells in PCOS Women

Polycystic ovary syndrome (PCOS) is often associated with metabolic syndrome features, including central obesity, suggesting that adipose tissue (AT) is a key organ in PCOS pathobiology. In this study, we compared both abdominal (ABD) and gluteofemoral (GF) subcutaneous AT in women with and without PCOS. ABD and GF subcutaneous ATs from PCOS and BMI/WHR-matched control women were analyzed by RT-qPCR, FACS and histology. ABD and GF adipose-derived stem cell (ASC) transcriptome and methylome were analyzed by RNA-seq and DNA methylation array. Similar to the control group with abdominal obesity, the GF AT of PCOS women showed lower expression of genes involved in lipid accumulation and angiogenesis compared to ABD depot. FACS analysis revealed an increase in preadipocytes number in both AT depots from PCOS. Further pathway analysis of RNA-seq comparisons demonstrated that the ASCs derived from PCOS are pro-inflammatory and exhibit a hypoxic signature in the ABD depot and have lower expression of adipogenic genes in GF depot. We also found a higher CpG methylation level in PCOS compared to control exclusively in GF-ASCs. Our data suggest that ASCs play an important role in the etiology of PCOS, potentially by limiting expansion of the healthy lower-body AT

Differential open chromatin profile and transcriptomic signature define depot-specific human subcutaneous preadipocytes: primary outcomes

Abstract Background Increased lower body fat is associated with reduced cardiometabolic risk. The molecular basis for depot-specific differences in gluteofemoral (GF) compared with abdominal (A) subcutaneous adipocyte function is poorly understood. In the current report, we used a combination of Assay for Transposase-Accessible Chromatin followed by sequencing (ATAC-seq), RNA-seq, and chromatin immunoprecipitation (ChIP)-qPCR analyses that provide evidence that depot-specific gene expression patterns are associated with differential epigenetic chromatin signatures. Methods Preadipocytes cultured from A and GF adipose tissue obtained from premenopausal apple-shaped women were used to perform transcriptome analysis by RNA-seq and assess accessible chromatin regions by ATAC-seq. We measured mRNA expression and performed ChIP-qPCR experiments for histone modifications of active (H3K4me3) and repressed chromatin (H3K27me3) regions respectively on the promoter regions of differentially expressed genes. Results RNA-seq experiments revealed an A-fat and GF-fat selective gene expression signature, with 126 genes upregulated in abdominal preadipocytes and 90 genes upregulated in GF cells. ATAC-seq identified almost 10-times more A-specific chromatin-accessible regions. Using a combined analysis of ATAC-seq and global gene expression data, we identified 74 of the 126 abdominal-specific genes (59%) with A-specific accessible chromatin sites within 200 kb of the transcription start site (TSS), including HOXA3, HOXA5, IL8, IL1b, and IL6. Interestingly, only 14 of the 90 GF-specific genes (15%) had GF-specific accessible chromatin sites within 200 kb of the corresponding TSS, including HOXC13 and HOTAIR, whereas 25 of them (28%) had abdominal-specific accessible chromatin sites. ChIP-qPCR experiments confirmed that the active H3K4me3 chromatin mark was significantly enriched at the promoter regions of HOXA5 and HOXA3 genes in abdominal preadipocytes, while H3K27me3 was less abundant relative to chromatin from GF. This is consistent with their A-fat specific gene expression pattern. Conversely, analysis of the promoter regions of the GF specific HOTAIR and HOXC13 genes exhibited high H3K4me3 and low H3K27me3 levels in GF chromatin compared to A chromatin. Conclusions Global transcriptome and open chromatin analyses of depot-specific preadipocytes identified their gene expression signature and differential open chromatin profile. Interestingly, A-fat-specific open chromatin regions can be observed in the proximity of GF-fat genes, but not vice versa. Trial registration Clinicaltrials.gov, NCT01745471. Registered 5 December 2012

Fat Distribution in Women Is Associated With Depot-Specific Transcriptomic Signatures and Chromatin Structure

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