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anne-emmanuelle berger is Professor of French Literature at Cornell University and Visiting Professor at the Centre de Recherches en Etudes Féminines at Paris VIII University. Her recent publications include Algeria in Others' Languages (Cornell University Press, 2002)and Scènes d'aumône: Misère et poésie au XIXe siècle (Champion, 2004). She is currently writing on Derrida.

Objective: This study was performed to analyze the modifications within adipose tissue during calorie restriction and more specifically to state whether hysteresis occurs during fat mass reduction. Method: Rats male Wistar increased their body weight by 130 g under control conditions and were then submitted to a calorie restriction (CR) at 30% or 60% of control. Experiment has been stopped when the body weight of the group CR60% returned back to its initial value. Samples of retroperitoneal adipose tissue were collected by biopsies along the study. Adipose cell size was analyzed using multisizer IV (Beckman Coulter) to determine the size distribution curves during natural growth and after calorie restriction. Results: After CR60%, body weights and adipose tissue masses were similar to the ones at the beginning of the experiment. Adipose cell size distribution curve was shifted to the left compared to the one of initial control. Adipose cell sizes were significantly lower after CR60% than those of control at the beginning of the experiment. Conclusions: These results state for the first time that hysteresis occurs in white adipose tissue after calorie restriction. The composition of adipose tissue after calorie restriction was significantly different than the one of initial control. After significant weight loss, organisms must be considered as different from the initial controls, they are most likely governed by different regulations which will have to be identified.

Obesity is linked to adipose tissue hypertrophy (increased adipocyte cell size) and hyperplasia (increased cell number). Comparative analyses of gene datasets allowed us to identify 1426 genes which may represent common adipose phenotype in humans and mice. Among them we identified several adipocyte-specific genes dysregulated in obese adipose tissue, involved in either fatty acid storage (acyl CoA synthase ACSL1, hormone-sensitive lipase LIPE, aquaporin 7 AQP7, perilipin PLIN) or cell adhesion (fibronectin FN1, collagens COL1A1, COL1A3, metalloprotein MMP9, or both (scavenger receptor FAT/CD36). Using real-time analysis of cell surface occupancy on xCELLigence system we developed a new method to study lipid uptake and differentiation of mouse 3T3L1 fibroblasts and human adipose stem cells. Both processes are regulated by insulin and fatty acids such as oleic acid. We showed that fatty acid addition to culture media increased the differentiation rate and was required for full differentiation into unilocular adipocytes. Significant activation of lipogenesis, i.e. lipid accumulation, by either insulin or oleic acid was monitored in times ranging from 1 to 24 h, depending on differentiation state, whereas significant effects on adipogenesis, i.e., surperimposed lipid accumulation and gene transcriptional regulations were measured after 3 to 4 d. Combination of selected times for analysis of lipid contents, cell counts, size fractionations, and gene transcriptional regulations showed that FAT/CD36 specific inhibitor AP5258 significantly increased cell survival of oleic acid-treated mouse and human adipocytes, and partially restored the transcriptional response to oleic acid in the presence of insulin through JNK pathway. Taken together, these data open new perspectives to study the molecular mechanisms commonly dysregulated in mouse and human obesity at the level of lipogenesis linked to hypertrophy and adipogenesis linked to hyperplasia.

International audience; The delivery of SiC-based nanoparticles (SiC-NPs) into living eukaryotic cells is facilitated in the presence of cell-penetrating peptides, both cationic (SAP) and anionic (SAP-E). The SiC-NP surface functional group modification combined with rational CPP selection introduces an additional mode of delivery control.

Cancer progression may be affected by metabolism. In this study, we aimed to analyze the effect of glucose on the proliferation and/or survival of human hepatocellular carcinoma (HCC) cells. Human gene datasets regulated by glucose were compared to gene datasets either dysregulated in HCC or regulated by other signaling pathways. Significant numbers of common genes suggested putative involvement in transcriptional regulations by glucose. Real-time proliferation assays using high (4.5 g/L)versuslow (1 g/L) glucose on two human HCC cell lines and specific inhibitors of selected pathways were used for experimental validations. High glucose promoted HuH7 cell proliferation but not that of HepG2 cell line. Gene network analyses suggest that gene transcription by glucose could be mediated at 92% through ChREBP in HepG2 cells, compared to 40% in either other human cells or rodent healthy liver, with alteration of LKB1 (serine/threonine kinase 11) and NOX (NADPH oxidases) signaling pathways and loss of transcriptional regulation of PPARGC1A (peroxisome-proliferator activated receptors gamma coactivator 1) target genes by high glucose. Both PPARA and PPARGC1A regulate transcription of genes commonly regulated by glycolysis, by the antidiabetic agent metformin and by NOX, suggesting their major interplay in the control of HCC progression.

Melanoma is the deadliest form of skin cancer owing to its proclivity to metastasise, and recently developed therapies have not yielded the expected results, because almost all patients relapse. Therefore, understanding the molecular mechanisms that underlie early invasion by melanoma cells is crucial to improving patient survival. We have previously shown that, whereas the Tetraspanin 8 protein (Tspan8) is undetectable in normal skin and benign lesions, its expression arises with the progression of melanoma and is sufficient to increase cell invasiveness. Therefore, to identify Tspan8 transcriptional regulators that could explain the onset of Tspan8 expression, thereby conferring an invasive phenotype, we performed an innovative RNA interference-based screen, which, for the first time, identified several Tspan8 repressors and activators, such as GSK3 beta, PTEN, IQGAP1, TPT1 and LCMR1. LCMR1 is a recently identified protein that is overexpressed in numerous carcinomas; its expression and role, however, had not previously been studied in melanoma. The present study identified Tspan8 as the first LCMR1 target that could explain its function in carcinogenesis. LCMR1 modulation was sufficient to positively regulate endogenous Tspan8 expression, with concomitant in vitro phenotypic changes such as loss of melanoma cell-matrix adherence and increase in invasion, and Tspan8 expression promoted tumourigenicity in vivo. Moreover, LCMR1 and Tspan8 overexpression were shown to correlate in melanoma lesions, and both proteins could be downregulated in vitro by vemurafenib. In conclusion, this study highlights the importance of Tspan8 and its regulators in the control of early melanoma invasion and suggests that they may be promising new therapeutic targets downstream of the RAF-MEK-ERK signalling pathway.

International audience; Introduction: Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods: Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results: The initial body weight of the rats was 46565.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion: Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues.

International audience; Exosomes are nanometer-sized microvesicles formed in multivesicular bodies (MVBs) during endosome maturation. Exosomes are released from cells into the microenvironment following fusion of MVBs with the plasma membrane. During the last decade, skeletal muscle-secreted proteins have been identified with important roles in intercellular communications. To investigate whether muscle-derived exosomes participate in this molecular dialog, we determined and compared the protein contents of the exosome-like vesicles (ELVs) released from C2C12 murine myoblasts during proliferation (ELV-MB), and after differentiation into myotubes (ELV-MT). Using a proteomic approach combined with electron microscopy, western-blot and bioinformatic analyses, we compared the protein repertoires within ELV-MB and ELV-MT. We found that these vesicles displayed the classical properties of exosomes isolated from other cell types containing components of the ESCRT machinery of the MVBs, as well as numerous tetraspanins. Specific muscle proteins were also identified confirming that ELV composition also reflects their muscle origin. Furthermore quantitative analysis revealed stage-preferred expression of 31 and 78 proteins in ELV-MB and ELV-MT respectively. We found that myotube-secreted ELVs, but not ELV-MB, reduced myoblast proliferation and induced differentiation, through, respectively, the down-regulation of Cyclin D1 and the up-regulation of myogenin. We also present evidence that proteins from ELV-MT can be incorporated into myoblasts by using the GFP protein as cargo within ELV-MT. Taken together, our data provide a useful database of proteins from C2C12-released ELVs throughout myogenesis and reveals the importance of exosome-like vesicles in skeletal muscle biology.

International audience; Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, a hormone excessively produced during obesity, is suggested to be involved in breast cancer. The aim of the study was to investigate procarcinogenic potential of leptin by evaluating influence of leptin on cell proliferation, cell cycle, apoptosis, and signaling on numerous breast cells lines, including 184B5 normal cells, MCF10A fibrocystic cells and MCF-7, MDA-MB-231, and T47D cancer cells. Expressions of leptin and Ob-R were analyzed using qRT-PCR and immunohistochemistry, proliferation using fluorimetric resazurin reduction test and xCELLigence system, apoptosis and cell cycle by flow cytometry, and effect of leptin on different signalling pathways using qRT-PCR and Western blot. Cells were exposed to increasing concentrations of leptin. All cell lines expressed mRNA and protein of leptin and Ob-R. Leptin stimulated proliferation of all cell lines except for 184B5 and MDA-MB-231 cells. Leptin inhibited apoptosis but didn't alter proportion of cells within cell cycle in MCF7 cells. Leptin induced overexpression of leptin, Ob-R, estrogen receptor, and aromatase mRNA in MCF-7 and T47D cells. Autoregulation induced by leptin, relationship with estrogen pathway, and proliferative and antiapoptic activity in breast cancer cells may explain that obesity-associated hyperleptinemia may be a breast cancer risk factor.

International audience; Hepatocellular carcinoma (HCC) represents one of the most frequently diagnosed human cancers; however, there are currently few treatment alternatives to surgical resection. In this study we performed bioinformatic analysis of previously published transcriptomic data in order to characterize liver specific networks, including biological functions, signaling pathways and transcription factors, potentially dysregulated in HCC. By incorporating specific signaling inhibitors into real-time proliferation assays using HepG2 cells, we then validated these in silico results. We found that G protein subunits Gi/G0, protein kinase C, Mek1/2, and Erk1/2 (P42/44), JAK1, PPARA and NFκB p65 subunit were the major signaling molecules required for survival and proliferation of human HCC cell lines. We also found that these pathways regulate the expression of key hepatic transcription factors involved in cell differentiation, such as CEBPA, EGR1, FOXM1 and PPARs. By combining bioinformatic and functional analyses, major signaling pathways related to tumorigenicity in HCC are revealed, thereby elucidating potential targets for drug therapies.

Berger E, Rome S, Vega N, Ciancia C, Vidal H. Transcriptome profiling in response to adiponectin in human cancer-derived cells. Physiol Genomics 42A: 61-70, 2010. First published June 22, 2010; doi:10.1152/physiolgenomics.00013.2010.-The adipocyte-derived hormone adiponectin exerts protective actions in several disorders, including some cancers. However, while growing data suggest that adiponectin could be an effective anticancer agent, its mechanism of action in cancer cells is still poorly known. Here, using microarrays, we identified a set of 1,301 genes commonly modulated in three cancer-derived cell lines in response to short-term stimulation with full-length recombinant human adiponectin. Most of these genes are involved in translation regulation, immune or stress responses, and cell proliferation. Furthermore, among genes linked to disease that were retrieved by functional enrichment tests using text mining based on PubMed analysis, we found that 66% are involved in malignant neoplasms, further supporting the link between adiponectin and cancer mechanisms. Bioinformatic analysis demonstrated the diversity of signaling pathways and transcription factors potentially mediating adiponectin effects on gene expression, illustrating the complexity of adiponectin mechanisms of action in cancer cells.

How and why do some contemporary body practices that take place at the crossroads of aesthetics and politics give to the critics of the sexual order a dimension that is both experiential and experimental? How do they produce meaning and effects that are susceptible of questioning the dominant rational order? These are the questions that guide the present research work. To answer them, I focus on a specific practice that operates as a tool to the feminist struggle: the drag king workshops. I propose here to analyze them at the light of a decentered reading of Antonin Artaud’s theater of cruelty. This reading relates the artaudian notion of cruelty to the notions of performance and performativity to highlight the creative and potentially subversive dimension of a corporal and collective practice. By relating aesthetic transformation and political engagement, this work on a “political travestying practice” explores the critical dimension of a kind of questioning our own corporal positions reflecting the scale of privileges and oppressions constituted by the dominant régime of rationality.My approach to these questions is also a situated approach, hence the autobiographic dimension of the process I propose here. Artaud has been a harsh critic of the logical and aesthetical forms of “western” rationality. That is why his reading can be useful to think the western closure. In fact, from my own position as a sudaka, a Colombian migrant, taken within a complex colonial history, I articulate, through my reading of Artaud’s thought and itinerary the critic of the sexual order and the critic of a dominant rationality. Faithful to a conception of the consubstantial connections between aesthetics and politics, as well as between practice and theory, I put on stage my encounter with Artaud and his own encounter with Mexico, a double encounter that informs my reading and my experience in the drag king workshops.; Comment et pourquoi certaines pratiques contemporaines du corps, qui se déroulent au carrefour de l’esthétique et du politique, donnent-elles à la critique de l’ordre sexuel une dimension à la fois vécue et expérimentale ? Comment produisent-elles un sens et des effets susceptibles de mettre en question l’ordre rationnel dominant ? Telles sont les questions qui guident ce travail de recherche. Pour y répondre, je me centre sur une pratique spécifique qui sert d’outil de lutte féministe : les ateliers drag king. Je propose de les analyser à la lumière d’une lecture décentrée du théâtre de la cruauté d’Antonin Artaud : il s’agit d’une lecture qui relie la notion artaudienne de cruauté à celles de performance et de performativité, afin de souligner la dimension créative et potentiellement subversive d’une pratique corporelle et collective. Ce travail sur un « travestissement politique » explore la dimension critique d’un certain questionnement de nos positions corporelles, là où celles-ci reflètent l’échelle des privilèges et des oppressions constituées par le régime de rationalité dominant.Mon approche de ces questions est une approche située, d’où la dimension autobiographique du parcours que je propose. Artaud a été un grand pourfendeur des formes logiques et esthétiques de la rationalité « occidentale ». C’est pourquoi il me semble que son expérience peut être utile pour penser la clôture occidentale. En effet, sa pensée et son itinéraire me permettent d’articuler ensemble critique de l’ordre du sexe et critique de la rationalité dominante, à partir de ma position de migrante sudaka, prise dans une histoire coloniale complexe. Fidèle à une conception du rapport consubstantiel entre esthétique et politique comme entre pratique et théorie, je mets en scène ma rencontre d’Artaud et sa propre rencontre avec le Mexique : double rencontre qui informe ma lecture et mon expérience des ateliers drag kings.

"Danse et genre : épistémologie d'un espace de recherche" constitue un mémoire de synthèse qui vise à tracer les contours d'un champ de recherches articulant études de genre et études en danse. L'objectif est de dégager un certain nombre d'éléments spécifiant cet espace encore peu développé en France, de poser des bases, ou du moins des jalons, afin de le baliser et de dégager des perspectives à poursuivre, également de faire une double généalogie des démarches et des études ayant abouti à sa constitution. Au-delà de ces objectifs, il y a l'enjeu d'en démontrer l'importance scientifique, notamment aux actrices et acteurs des deux pôles, et de sortir d'une méconnaissance réciproque. Le mémoire comporte quatre chapitres. 1. "Introduction et cadres généraux" présente le concept de genre et la position théorique où je me situe, l' "objet" danse – en se gardant bien de le définir – et quelques aspects spécifiques des études en danse, avant de tenter de cerner un champ méthodologique défini, non pas a priori, mais construit de façon pragmatique au fil du parcours et focalisé sur une pratique de l'inter et de la trans -disciplinarité, justifiée par la double complexité des objets et des problématiques posées, mais résultant aussi d'un choix et d'une expérience personnelle de la recherche. 2. Partout et depuis presque toujours, la danse est une activité et un art marqués par le genre, au point qu'il n'est guère possible de l'étudier d'un point de vue historique ou anthropologique sans introduire cette dimension qui structure ses pratiques. Le deuxième chapitre, "Danse et genre, croisements féconds", présente trois perspectives pour envisager les liens entre danse et genre. La première et la plus fondamentale a trait à la façon dont le genre travaille les matières de la danse et dont, réciproquement, ces matières travaillent le genre, que ce soit pour participer à sa stabilité et à sa légitimité ou, à l'inverse, en perturbant ses processus et en s'y opposant. La deuxième perspective, sous un angle plus sociologique, présente quelques effets du genre dans le secteur chorégraphique en France, à l'heure actuelle. Enfin, découlant de ce qui précède, la troisième évoque les croisements possibles, souhaitables, entre recherches en danse et recherches en genre.3. Le chapitre "Questionnements croisés dans les pratiques et les savoirs - Contextes anglo-saxon et français" permet d'esquisser une généalogie de l'espace constitué, en s'intéressant à la façon dont les questions féministes et de genre ont pénétré le champ des pratiques et celui des recherches en danse, et réciproquement à celle dont la danse a – ou n'a pas – investi le champ des pratiques comme des recherches féministes. Une telle étude ne peut manquer de s'intéresser aux différences culturelles entre la France et les pays anglo-saxons.4. Enfin, "La catégorisation féminine de la danse, paradigme du genre", est un chapitre consacré à une question fondamentale et préalable à toute autre recherche, celle de la représentation symbolique de la danse comme féminine, représentation qui biaise une grande partie des approches et pèse lourdement, tant sur le secteur des pratiques chorégraphiques que sur la recherche. Il s'agit de s'interroger sur les sources de cette catégorisation analysée comme paradigmatique des mécanismes de catégorisation de genre, induite par des processus de hiérarchisation, d'exclusion et de constitution d'une altérité au modèle masculin.

"Histoire et esthétique de la danse de ballet au XIXe siècle - Quelques aspects au prisme du genre, féminisation du ballet et stigmatisation des danseurs" est une synthèse de travaux sur la danse de ballet au XIXe siècle, à partir d'une problématique initiale concernant la fixation de la féminisation - à la fois symbolique et des pratiques - de la danse. Quatre chapitres et un divertissement composent ce mémoire. Le premier chapitre porte sur la question des sources et des spécificités des matériaux dont disposent les chercheuses et chercheurs en danse, sur les récits historiques qui souvent, loin de pouvoir constituer la base de recherches actuelles, se révèlent être des pièges, confondant représentations sociales et faits historiques ; ce phénomène relève essentiellement de biais liés au genre/gender.Le deuxième présente les éléments factuels nécessaires à la compréhension de l'émergence et des évolutions du ballet-pantomime romantique, son cadre institutionnel et ses publics, les principales œuvres qui font repères. Un troisième chapitre interroge les spécificités du ballet-pantomime, pour comprendre sa place dans l'histoire de la danse et du Romantisme. Il aborde les enjeux esthétiques auxquels la danse a été confrontée au XIXe siècle, la façon dont elle a évolué dans un réseau de redéfinitions des arts et des artistes, pour tendre vers une autonomie simultanément artistique et comme champ social. Les nouvelles valeurs et redéfinitions s'articulent de plusieurs façons à des problématiques de genre ; elles orientent à différents niveaux la féminisation du ballet et la stigmatisation des danseurs.Le chapitre suivant, "l'esprit du temps : la féminisation symbolique et professionnelle du ballet", traite la question initiale et centrale des dynamiques et des modalités avec lesquelles le contexte a provoqué, en quelques années, un changement profond dans les représentations sociales de la danse de ballet, essentialisée en art féminin où un homme n'était plus légitime. Pour clore ces recherches, en guise de "divertissement", figure une recherche sur le ballet La Révolte au sérail ou La Révolte des femmes, de 1833, seul ballet-pantomime romantique à faire référence à des évènements politiques de son temps et à mettre en scène des revendications féministes.

My dissertation explores the ways feminists mobilize the notion of "the universal" in their claims for justice. Since the late 1950s, the use of universalism in feminist discourse, whether claimed or latent, has been highly criticized. Namely, this critique highlights the ethnocentric, imperialist, and patriarchal philosophical framework underlying this discourse that was inherited from Enlightenment theory. In recent years, queer and postcolonial feminisms have expanded on this critique, urging feminists to explore ethical and contextual approaches while distancing themselves from the rhetoric of (universal) human rights. I argue in this dissertation that, despite the importance of these various critiques, we must retain "the universal" as a horizon for feminist theories of justice. Beginning with the hypothesis that "the universal" is always ambiguous, or equivocal, I argue that nonetheless it can still play an important role, at both the political and intersubjective levels. To think of "the universal" as an ambiguous concept enables us to reconceive the subject itself, as well as a postmodern ethics in light of queer and postcolonial critiques. After examining both feminist critiques that were addressed to some theories of justice (in particular Rawls') and feminist ethical debates (including ethics of care or ecofeminist ethics), I suggest the possibility of articulating a feminist ethic with a theory of fair or just institutions. My claim is that, while maintaining the ambiguity of "the universal," such a conception of justice helps us not only to conceive new forms of transnational solidarities, but also to rethink the terms of a feminist cosmopolitanism., Ce travail explore la façon dont les féministes mobilisent la notion d'universel dans leurs revendications de justice. Depuis les années 1950, l'universalisme latent ou assumé de certains discours féministes a été beaucoup critiqué. On a reproché à ces discours de se déployer dans les cadres philosophiques à la fois ethnocentriques, impérialistes et patriarcaux hérités des Lumières. Ces critiques, qui sont principalement relayées, depuis quelques années, par les féminismes queer et postcoloniaux, ont conduit certaines féministes à prendre leurs distances avec la rhétorique des droits universels, et à privilégier des approches éthiques et contextualistes. Tout en parcourant la diversité de ces critiques, ma thèse examine la possibilité de maintenir l'universel à l'horizon d'une théorie féministe de la justice. Partant de l'intuition selon laquelle l'universel est d'emblée ambigu, ou équivoque, je suggère qu'il est possible de le conserver comme un horizon des luttes féministes, au niveau intersubjectif comme au niveau politique. Concevoir l'universel comme ambigu offre selon moi la possibilité de repenser le sujet et les éthiques postmodernes à la lumière des critiques adressées par les féministes queer et postcoloniales. Après avoir examiné les critiques féministes adressées à certaines théories de la justice (principalement celle de Rawls), mais également les débats féministes en matière d'éthique (éthiques du care, ou éthiques écoféministes par exemple), je propose d'articuler une éthique féministe à une théorie politique des institutions justes. Tout en maintenant l'ambigüité de l'universel, cette conception de la justice permet non seulement de concevoir de nouvelles formes de solidarités transnationales mais aussi de repenser les termes d'un cosmopolitisme féministe.