Virginie Bourlier

Paul Sabatier University - Toulouse III, Tolosa de Llenguadoc, Midi-Pyrénées, France

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Publications (28)151.19 Total impact

  • C Laurens · K Louche · C Sengenes · M Coué · D Langin · C Moro · V Bourlier
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    ABSTRACT: Background/objectives: Recent reports indicate that inter/intramuscular adipose tissue (IMAT), composed by adipocytes underneath the deep fascia of muscles, is positively correlated with aging, obesity and insulin resistance in humans. However no molecular/cellular evidence is available to support these interactions. The current study aimed to better characterize human skeletal muscle-derived adipogenic progenitors obtained from obese volunteers and investigate the impact of derived adipocytes on insulin action in primary skeletal muscle cells. Methods: Primary cultured stroma-vascular fraction (SVF) obtained from vastus lateralis muscle biopsies of middle-aged obese subjects was immuno-separated (magnetic beads or flow cytometry). The characteristics and/or metabolic phenotype of CD56(+), CD56(-) and CD56(-)CD15(+) cellular fractions were investigated by complementary approaches (flow cytometry, cytology, qPCR and metabolic assays). The effects of conditioned media from CD56(-)CD15(+) cells, differentiated into adipocytes, on insulin action and signaling in human primary myotubes was also examined. Results: Our data indicate that CD56(+) and CD56(-) cellular fractions isolated from cultured SVF of human muscle contain two distinct committed progenitors, CD56(+) cells (i.e., satellite cells) as myogenic progenitors and CD15(+) cells as adipogenic progenitors, respectively. CD56(-)CD15(+)-derived adipocytes display the phenotype and metabolic properties of white adipocytes. Secretions of CD56(-)CD15(+) cells differentiated into functional white adipocytes reduced insulin-mediated non oxidative glucose disposal (P=0.0002) and insulin signaling. Conclusions: Using in vitro models, we show for the first time that secretions of skeletal muscle adipocytes are able to impair insulin action and signaling of muscle fibers. This paracrine effect could explain, at least in part, the negative association between high levels of IMAT and insulin sensitivity in obesity and aging.International Journal of Obesity accepted article preview online, 23 September 2015. doi:10.1038/ijo.2015.193.
    No preview · Article · Sep 2015 · International journal of obesity (2005)
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    Cedric Moro · Virginie Bourlier

    Preview · Article · Sep 2015 · Diabetes
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    ABSTRACT: Circulating natriuretic peptide (NP) levels are reduced in obesity and predict the risk of type 2 diabetes (T2D). Since skeletal muscle was recently shown as a key target tissue of NP, we aimed to investigate muscle NP receptor (NPR) expression in the context of obesity and T2D. Muscle NPRA correlated positively with whole-body insulin sensitivity in humans, and was strikingly down-regulated in obese subjects and recovered in response to diet-induced weight loss. In addition, muscle NP clearance receptor (NPRC) increased in individuals with impaired glucose tolerance and T2D. Similar results were found in obese diabetic mice. Although no acute effect of brain-NP (BNP) on insulin sensitivity was observed in lean mice, chronic BNP infusion improved blood glucose control and insulin sensitivity in skeletal muscle of obese and diabetic mice. This occurred in parallel of a reduced lipotoxic pressure in skeletal muscle due to an up-regulation of lipid oxidative capacity. In addition, chronic NP treatment in human primary myotubes increased lipid oxidation in a PGC1α-dependent manner and reduced palmitate-induced lipotoxicity. Collectively, our data show that activation of NPRA signaling in skeletal muscle is important for the maintenance of long-term insulin sensitivity and has the potential to treat obesity-related metabolic disorders. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    No preview · Article · Aug 2015 · Diabetes
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    ABSTRACT: Introduction La régulation des cellules T dans le tissu adipeux constitue un lien important entre l’inflammation et l’insulino-résistance. Nous avons recherché les cellules présentatrices d’antigènes dans le tissu adipeux des souris et patients obèses en fonction de l’insulino-résistance. Patients et méthodes Les cellules dendritiques ont été étudiées dans le tissu adipeux de souris minces, obèses (HFD), Rag1–/–, de 20 patients avec des IMC allant de 19,5 à 38 kg/m2, ainsi que des patients obèses morbides sans (n = 10) ou avec un diabète de type 2 (n = 110) par des approches de cytométrie en flux et PCR quantitative Résultats Chez la souris mince, la présence des CDs résidantes (CD11chighF4/80neg) est détectée dans le tissu adipeux epididymaire. Chez des souris déficientes en cellules T, le transfert adoptif de cellules T naïve spécifique à l’ovalbumine induit majoritairement une réponse de type Th1 en réponse à l’ovalbumine dans le tissu adipeux. Dans les souris et patients obèses, les CDs (CD11c+CD1c+ chez l’homme et CD11chighF4/80lowCX3CR1pos chez la souris) sont majoritairement accumulées dans le tissu adipeux. Les CDs CD11chighF4/80low isolées chez les souris obèses induisent, ex-vivo, la polarisation des cellules T naïves en cellules Th17. Dans une cohorte de 20 patients, le nombre de cellules CD1c+CD11c+ par g de tissu adipeux sous-cutanés est corrélé à IMC (rs = 10,4947; P < 0,05). Chez des patients obèses morbides, l’expression génique de CD1c dans la tissu adipeux sous-cutané est plus importante chez les patients diabétiques versus les patients obèses, et est corrélé à HOMA-IR (rs = 10,560; P = 10,013). Conclusion Nous montrons, pour la première fois, la présence et l’accumulation des CDs dans le tissu adipeux en fonction de l’obésité et de l’insulino-résistance chez la souris et les patients. Ces cellules dendritiques sont fonctionnelles et pourraient favoriser la polarisation des cellules T en Th1 et Th17 dans le tissu adipeux inflammé.
    No preview · Conference Paper · May 2014
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    ABSTRACT: j.celrep.2014.03.062 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). SUMMARY Adipose tissue fibrosis development blocks adipo-cyte hypertrophy and favors ectopic lipid accumula-tion. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in hu-mans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte meta-bolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a func-tional Toll-like receptor 4 on adipose tissue hemato-poietic cells is necessary for the initiation of adipose tissue fibrosis. Continuous low-dose infusion of the Toll-like receptor 4 ligand, lipopolysaccharide, pro-motes adipose tissue fibrosis. Ex vivo, lipopolysac-charide-mediated induction of fibrosis is prevented by antibodies against the profibrotic factor TGFb1. Together, these results indicate that obesity and en-dotoxemia favor the development of adipose tissue fibrosis, a condition associated with insulin resis-tance, through immune cell Toll-like receptor 4. INTRODUCTION
    Full-text · Dataset · May 2014
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    ABSTRACT: Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte metabolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a functional Toll-like receptor 4 on adipose tissue hematopoietic cells is necessary for the initiation of adipose tissue fibrosis. Continuous low-dose infusion of the Toll-like receptor 4 ligand, lipopolysaccharide, promotes adipose tissue fibrosis. Ex vivo, lipopolysaccharide-mediated induction of fibrosis is prevented by antibodies against the profibrotic factor TGFβ1. Together, these results indicate that obesity and endotoxemia favor the development of adipose tissue fibrosis, a condition associated with insulin resistance, through immune cell Toll-like receptor 4.
    Full-text · Article · Apr 2014 · Cell Reports
  • C. Laurens · P.-M. Badin · K. Louche · D. Langin · V. Bourlier · C. Moro
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    ABSTRACT: Introduction Les triglycérides intramusculaires constituent une source d’énergie importante pour le muscle squelettique notamment au cours d’un exercice physique. Des travaux récents suggèrent que l’ATGL (adipose triglyceride lipase) joue un rôle clé dans ce processus. Cependant, peu de données sont actuellement disponibles sur le contrôle de son activité. L’objectif de ce travail était d’étudier le rôle de la protéine G0/G1 Switch Gene 2 (G0S2), récemment décrite comme inhibitrice de l’ATGL dans le tissu adipeux, dans la régulation de la lipolyse et du métabolisme oxydatif musculaire. Matériels et méthodes L’expression de G0S2 a été diminuée, à l’aide de lentivirus contenant des shRNA, dans des cultures primaires de cellules musculaires squelettiques humaines (i.e. myotubes) issues de biopsies de rectus abdominis obtenues chez des volontaires sains. L’activité de l’ATGL, le contenu en triglycérides, la mobilisation et l’oxydation des acides gras, l’oxydation du glucose et la synthèse de glycogène ont été évalués à l’aide de substrats radiomarqués. Les approches métaboliques ont été complétées par des études d’immunofluorescence des mitochondries et d’expression de gènes clés par RT-qPCR. Résultats Nos résultats montrent que G0S2 est exprimé dans les myotubes et qu’il inhibe l’activité de l’ATGL. Son invalidation induit une diminution du pool de triglycérides et une augmentation de la mobilisation et de l’oxydation des acides gras. L’oxydation du glucose et la synthèse de glycogène sont diminuées. L’augmentation du flux d’acides gras s’accompagne d’une hausse de la masse et du potentiel de membrane des mitochondries. Ces effets seraient potentiellement médiés par l’induction de gènes cibles du Peroxysome Proliferator Activated Receptor δ (PPARδ). Conclusion Ces résultats indiquent que G0S2 joue un rôle majeur dans la régulation de la lipolyse et du métabolisme oxydatif musculaire, en modulant le flux d’acides gras et l’expression de gènes cibles de PPARδ.
    No preview · Article · Mar 2014 · Diabetes & Metabolism
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    ABSTRACT: The aim of the present study was to investigate the influence of substrate availability on fuel selection during exercise. Eight endurance-trained male cyclists performed 90-min exercise at 70 % of their maximal oxygen uptake in a cross-over design, either in rested condition (CON) or the day after 2-h exercise practised at 70 % of maximal oxygen uptake (EX). Subjects were given a sucrose load (0.75 g kg−1 body weight) 45 min after the beginning of the 90-min exercise test. Lipolysis was measured in subcutaneous abdominal adipose tissue (SCAT) by microdialysis and substrate oxidation by indirect calorimetry. Lipid oxidation increased during exercise and tended to decrease during sucrose ingestion in both conditions. Lipid oxidation was higher during the whole experimental period in the EX group (p = 0.004). Interestingly, fuel selection, assessed by the change in respiratory exchange ratio (RER), was increased in the EX session (p = 0.002). This was paralleled by a higher rate of SCAT lipolysis reflected by dialysate glycerol, plasma glycerol, and fatty acids (FA) levels (p < 0.001). Of note, we observed a significant relationship between whole-body fat oxidation and dialysate glycerol in both sessions (r 2 = 0.33, p = 0.02). In conclusion, this study highlights the limiting role of lipolysis and plasma FA availability to whole-body fat oxidation during exercise in endurance-trained subjects. This study shows that adipose tissue lipolysis is a determinant of fuel selection during exercise in healthy subjects.
    No preview · Article · Dec 2013 · Journal of physiology and biochemistry
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    ABSTRACT: Context:Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesity-related metabolic disorders.Objectives:The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects.Design and Volunteers:Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training.Main Outcome Measures:Clinical characteristics and ex vivo substrate oxidation rates were measured pre- and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated.Results:Our data show that exercise training reduced IMTG content by 42% (P < .01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive-lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G0/G1 switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001).Conclusions:Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity.
    No preview · Article · Oct 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Context:It was suggested that human cultured primary myotubes retain the metabolic characteristics of their donor in vitro.Objectives:The aim of the present study was to investigate whether the metabolic responses to endurance training are also conserved in culture.Design and Volunteers:Middle-aged obese subjects completed an 8-week supervised aerobic exercise training program in which vastus lateralis muscle biopsies were collected before and after training.Main Outcome Measures:Anthropometric and blood parameters, as well as aerobic capacity, were assessed before and after training. Muscle biopsies were either used for Western blot analysis or digested to harvest myogenic progenitors that were differentiated into myotubes. Glucose oxidation, palmitate oxidation, and glycogen synthesis assays were performed on myotubes before and after training. Gene expression was assessed by real-time quantitative PCR.Results:Our data indicate that in parallel of in vivo improvement of whole-body aerobic capacity and glucose metabolism, biopsy-derived primary myotubes showed similar patterns in vitro. Indeed, glucose oxidation, glycogen synthesis, and inhibition of palmitate oxidation by glucose were enhanced in myotubes after training. This was associated with consistent changes in the expression of metabolism-linked genes such as GLUT1, PDK4, and PDHA1. Interestingly, no difference in myogenic differentiation capacity was observed before and after training.Conclusion:Aerobic exercise training is associated with metabolic adaptations in vivo that are preserved in human cultured primary myotubes. It can be hypothesized that skeletal muscle microenvironmental changes induced by endurance training lead to metabolic imprinting on myogenic progenitor cells.
    No preview · Article · Jul 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Elevated expression/activity of adipose triglyceride lipase (ATGL) and/or reduced activity of hormone-sensitive lipase (HSL) in skeletal muscle are causally linked to insulin resistance in vitro. We investigated here the effect of high-fat feeding on skeletal muscle lipolytic proteins, lipotoxicity, and insulin signaling in vivo. Five-week-old C3H mice were fed normal chow diet (NCD) or 45% kcal high-fat diet (HFD) for 4 weeks. Wild-type and HSL knockout mice fed NCD were also studied. Whole-body and muscle insulin sensitivity, as well as lipolytic protein expression, lipid levels, and insulin signaling in skeletal muscle, were measured. HFD induced whole-body insulin resistance and glucose intolerance and reduced skeletal muscle glucose uptake compared with NCD. HFD increased skeletal muscle total diacylglycerol (DAG) content, protein kinase Cθ and protein kinase Cε membrane translocation, and impaired insulin signaling as reflected by a robust increase of basal Ser1101 insulin receptor substrate 1 phosphorylation (2.8-fold, P < .05) and a decrease of insulin-stimulated v-Akt murine thymoma viral oncogene homolog Ser473 (-37%, P < .05) and AS160 Thr642 (-47%, P <.01) phosphorylation. We next showed that HFD strongly reduced HSL phosphorylation at Ser660. HFD significantly up-regulated the muscle protein content of the ATGL coactivator comparative gene identification 58 and triacylglycerol hydrolase activity, despite a lower ATGL protein content. We further show a defective skeletal muscle insulin signaling and DAG accumulation in HSL knockout compared with wild-type mice. Together, these data suggest a pathophysiological link between altered skeletal muscle lipase expression and DAG-mediated insulin resistance in mice.
    Full-text · Article · Mar 2013 · Endocrinology
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    ABSTRACT: Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPARγ coactivator-1α (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in response to aerobic exercise training in human skeletal muscle. In human myotubes, NP induced PGC-1α and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression, fat oxidation, and maximal respiration independent of substantial changes in mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated the effect of exercise training on muscle fat oxidative capacity in vivo. Collectively, these data show that activation of NP signaling in human skeletal muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose that NP could contribute to exercise training-induced improvement in skeletal muscle fat oxidative capacity in humans.
    Preview · Article · Nov 2012 · The Journal of clinical investigation
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    ABSTRACT: Leukotrienes (LTs) are potent proinflammatory mediators, and many important aspects of innate and adaptive immune responses are regulated by LTs. Key members of the LT synthesis pathway are overexpressed in adipose tissue (AT) during obesity, resulting in increased LT levels in this tissue. We observed that several mouse adipocyte cell lines and primary adipocytes from mice and humans both can secrete large amounts of LTs. Furthermore, this production increases with a high-fat diet (HFD) and positively correlates with adipocyte size. LTs produced by adipocytes play an important role in attracting macrophages and T cells in in vitro chemotaxis assays. Mice that are deficient for the enzyme 5-lipoxygenase (5-LO), and therefore lack LTs, exhibit a decrease in HFD-induced AT macrophage and T-cell infiltration and are partially protected from HFD-induced insulin resistance. Similarly, treatment of HFD-fed wild-type mice with the 5-LO inhibitor Zileuton also results in a reduction of AT macrophages and T cells, accompanied by a decrease in insulin resistance. Together, these findings suggest that LTs represent a novel target in the prevention or treatment of obesity-associated inflammation and insulin resistance.
    Full-text · Article · Jun 2012 · Diabetes
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    ABSTRACT: T-cell regulation in adipose tissue provides a link between inflammation and insulin resistance. Because of alterations in adipose tissue T-cell composition in obesity, we aimed to identify the antigen-presenting cells in adipose tissue of obese mice and patients with insulin resistance. Dendritic cells (DCs) and T cells were studied in mice and in two cohorts of obese patients. In lean mice, only CD11c(+) DCs were detected in adipose tissue. Adoptive transfer of naive CD4(+) T cells in Rag1(-/-) mice led to a predominant Th1 response in adipose tissue. In contrast, during obesity DCs (human CD11c(+)CD1c(+) and mouse CD11c(high)F4/80(low)) accumulated in adipose tissue. CD11c(high)F4/80(low) DCs from obese mice induced Th17 differentiation. In patients, the presence of CD11c(+)CD1c(+) DCs correlated with the BMI and with an elevation in Th17 cells. In addition, these DCs led to ex vivo Th17 differentiation. CD1c gene expression further correlated with homeostatic model assessment-insulin resistance in the subcutaneous adipose tissue of obese patients. We show for the first time the presence and accumulation of specific DCs in adipose tissue in mouse and human obesity. These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance.
    Full-text · Article · May 2012 · Diabetes
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    ABSTRACT: Objectif Nous avons étudié le rôle du co-activateur de l’adipose triglyceride lipase, CGI-58 (Comparative Gene Identification-58) dans le métabolisme énergétique du muscle squelettique. Matériels et méthodes Nous avons d’abord étudié l’expression de CGI-58 dans divers types de muscles chez la souris. Ensuite nous avons évalué les effets d’un gain ou d’une perte de fonction de CGI-58 sur le métabolisme lipidique, glucidique et oxydatif de cultures primaires de cellules musculaires humaines. Pour cela nous avons mesuré, dans ces cellules, le flux lipolytique, l’oxydation des acides gras (AG) ou du glucose et l’expression de gènes oxydatifs. Résultats Nous avons observé chez la souris que CGI-58 était préférentiellement exprimé dans les muscles oxydatifs qui possèdent une forte activité d’hydrolyse des triacylglycérols (TAG). Nous avons également montré qu’une surexpression de CGI-58 augmentait de plus de 2 fois l’hydrolyse des TAG, ainsi que le relargage et l’oxydation des AG dérivants des TAG. À l’inverse une invalidation ciblée de CGI-58 diminue l’hydrolyse des TAG, le flux intracellulaire d’AG et leur oxydation (− 77%, p < 0,001). Nous avons constaté en parallèle une augmentation de l’oxydation du glucose et de la synthèse de glycogène dans les myotubes invalidés pour CGI-58. Nous montrons également que le flux d’AG issu de la lipolyse module spécifiquement l’expression de gènes cibles de PPAR-δ (peroxisome proliferator activating receptor-δ) comme PDK4 (pyruvate dehydrogenase kinase 4) gène impliqué dans la régulation de l’oxydation du glucose. Conclusion Nos résultats démontrent un rôle important de CGI-58 dans le contrôle du métabolisme lipidique, glucidique et oxydatif du muscle squelettique.
    No preview · Article · Mar 2012 · Diabetes & Metabolism

  • No preview · Article · Mar 2012 · Diabetes & Metabolism
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    ABSTRACT: We investigated here the specific role of CGI-58 in the regulation of energy metabolism in skeletal muscle. We first examined CGI-58 protein expression in various muscle types in mice, and next modulated CGI-58 expression during overexpression and knockdown studies in human primary myotubes and evaluated the consequences on oxidative metabolism. We observed a preferential expression of CGI-58 in oxidative muscles in mice consistent with triacylglycerol hydrolase activity. We next showed by pulse-chase that CGI-58 overexpression increased by more than 2-fold the rate of triacylglycerol (TAG) hydrolysis, as well as TAG-derived fatty acid (FA) release and oxidation. Oppositely, CGI-58 silencing reduced TAG hydrolysis and TAG-derived FA release and oxidation (-77%, P < 0.001), whereas it increased glucose oxidation and glycogen synthesis. Interestingly, modulations of CGI-58 expression and FA release are reflected by changes in pyruvate dehydrogenase kinase 4 gene expression. This regulation involves the activation of the peroxisome proliferator activating receptor-δ (PPARδ) by lipolysis products. Altogether, these data reveal that CGI-58 plays a limiting role in the control of oxidative metabolism by modulating FA availability and the expression of PPARδ-target genes, and highlight an important metabolic function of CGI-58 in skeletal muscle.
    Preview · Article · Feb 2012 · The Journal of Lipid Research
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    ABSTRACT: The present study was undertaken to characterize the remodeling phenotype of human adipose tissue (AT) macrophages (ATM) and to analyze their paracrine effects on AT progenitor cells. The phenotype of ATM, immunoselected from subcutaneous (Sc) AT originating from subjects with wide range of body mass index and from paired biopsies of Sc and omental (Om) AT from obese subjects, was studied by gene expression analysis in the native and activated states. The paracrine effects of ScATM on the phenotype of human ScAT progenitor cells (CD34(+)CD31(-)) were investigated. Two main ATM phenotypes were distinguished based on gene expression profiles. For ScAT-derived ATM, obesity and adipocyte-derived factors favored a pro-fibrotic/remodeling phenotype whereas the OmAT location and hypoxic culture conditions favored a pro-angiogenic phenotype. Treatment of native human ScAT progenitor cells with ScATM-conditioned media induced the appearance of myofibroblast-like cells as shown by expression of both α-SMA and the transcription factor SNAIL, an effect mimicked by TGFβ1 and activinA. Immunohistochemical analyses showed the presence of double positive α-SMA and CD34 cells in the stroma of human ScAT. Moreover, the mRNA levels of SNAIL and SLUG in ScAT progenitor cells were higher in obese compared with lean subjects. Human ATM exhibit distinct pro-angiogenic and matrix remodeling/fibrotic phenotypes according to the adiposity and the location of AT, that may be related to AT microenvironment including hypoxia and adipokines. Moreover, human ScAT progenitor cells have been identified as target cells for ScATM-derived TGFβ and as a potential source of fibrosis through their induction of myofibroblast-like cells.
    Full-text · Article · Feb 2012 · PLoS ONE
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    ABSTRACT: Our goal was to identify a set of human adipose tissue macrophage (ATM)-specific markers and investigate whether their gene expression in subcutaneous adipose tissue (SAT) as well as in visceral adipose tissue (VAT) is related to obesity and to the occurrence of the metabolic syndrome. ATM-specific markers were identified by DNA microarray analysis of adipose tissue cell types isolated from SAT of lean and obese individuals. We then analysed gene expression of these markers by reverse transcription quantitative PCR in paired samples of SAT and VAT from 53 women stratified into four groups (lean, overweight, obese and obese with the metabolic syndrome). Anthropometric measurements, euglycaemic-hyperinsulinaemic clamp, blood analysis and computed tomography scans were performed. A panel of 24 genes was selected as ATM-specific markers based on overexpression in ATM compared with other adipose tissue cell types. In SAT and VAT, gene expression of ATM markers was lowest in lean and highest in the metabolic syndrome group. mRNA levels in the two fat depots were negatively correlated with glucose disposal rate and positively associated with indices of adiposity and the metabolic syndrome. In humans, expression of ATM-specific genes increases with the degree of adiposity and correlates with markers of insulin resistance and the metabolic syndrome to a similar degree in SAT and in VAT.
    Full-text · Article · Apr 2011 · Diabetologia
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    ABSTRACT: By the 1960s, the research of Tedeschi, Wasserman, and Liebelt had pointed out that adipose tissue (AT) is not solely composed by fat cells or adipocytes but also by various stromal cells, resident and infiltrating immune cells, and an extensive endothelial network. Collectively, these cells are referred to as the stroma-vascular fraction of AT (AT-SVF). The physiological growth of AT, which occurs throughout normal development but also as a result of fat mass excessive enlargement associated with obesity, involves the remodeling of AT cell compartments, the adipocytes, and the SVF. Indeed, although it is well described that adipocytes, which are the site of AT metabolic activity, are able to adapt their size but also their number to maintain energy homeostasis, the cells from the SVF also appear to play an important role in the growth of AT. This chapter focuses on the changes occurring in AT during normal and excessive fat mass growth, including changes in adipocyte number and size and SVF cellular remodeling.
    No preview · Article · Jan 2011

Publication Stats

792 Citations
151.19 Total Impact Points

Institutions

  • 2009-2015
    • Paul Sabatier University - Toulouse III
      • Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse - UMRS 1048 - I2MC
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2008-2015
    • University of Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2008-2014
    • French Institute of Health and Medical Research
      • Institute of Metabolic and Cardiovascular Diseases I2MC
      Lutetia Parisorum, Île-de-France, France