Dominique Langin

French Institute of Health and Medical Research, Lutetia Parisorum, Île-de-France, France

Are you Dominique Langin?

Claim your profile

Publications (264)1364.89 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectiveα-Lipoic acid (α-LA) is a natural occurring antioxidant with beneficial effects on obesity. The aim of this study was to investigate the putative effects of α-LA on triglyceride accumulation and lipogenesis in subcutaneous adipocytes from overweight/obese subjects and to determine the potential mechanisms involved.Design and Methods Fully differentiated human subcutaneous adipocytes were treated with α-LA (100 and 250 µM) during 24 h for studying triglyceride content, de novo lipogenesis, and levels of key lipogenic enzymes. The involvement of AMP-activated protein kinase (AMPK) activation was also evaluated.Resultsα-LA down-regulated triglyceride content by inhibiting fatty acid esterification and de novo lipogenesis. These effects were mediated by reduction in fatty acid synthase (FAS), stearoyl-coenzyme A desaturase 1, and diacylglycerol O-acyltransferase 1 protein levels. Interestingly, α-LA increased AMPK and acetyl CoA carboxylase phosphorylation, while the presence of the AMPK inhibitor Compound C reversed the inhibition observed on FAS protein levels.Conclusionsα-LA down-regulates key lipogenic enzymes, inhibiting lipogenesis and reducing triglyceride accumulation through the activation of AMPK signaling pathway in human subcutaneous adipocytes from overweight/obese subjects.
    Obesity 07/2014; · 3.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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.
    Cell Reports 04/2014; · 7.21 Impact Factor
  • Peter Arner, Dominique Langin
    [Show abstract] [Hide abstract]
    ABSTRACT: Triglycerides in adipose tissue are rapidly mobilized during times of energy needs via lipolysis, a catabolic process that plays important role in whole body triglyceride turnover. Lipolysis is regulated through cell surface receptors via neurotransmitters, hormones, and paracrine factors that activate various intracellular pathways. These pathways converge on the lipid droplet, the site of action of lipases and cofactors. Fat cell lipolysis is also involved in the pathogenesis of metabolic disorders, and recent human studies have underscored its role in disease states such as cancer cachexia and obesity-induced insulin resistance. We highlight here topics and findings with physiological and clinical relevance, namely lipid turnover in human fat cells and the role of lipolysis in cancer cachexia and obesity-induced insulin resistance.
    Trends in Endocrinology and Metabolism 04/2014; · 8.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To investigate if inulin-type fructan (ITF) prebiotics could counteract the thiazolidinedione (TZD, PPARγ activator) induced-fat mass gain, without affecting its beneficial effect on glucose homeostasis, in high-fat (HF) diet fed mice. Design and Methods: Male C57bl6/J mice were fed a HF diet alone or supplemented with ITF prebiotics (0.2g/day*mouse) or TZD (30mg pioglitazone/kg body weight*day) or both during 4 weeks. An insulin tolerance test was performed after 3 weeks of treatment. Results: As expected, pioglitazone improved glucose homeostasis and increased adiponectinaemia. Furthermore, it induced an over-expression of several PPARγ target genes in white adipose tissues. ITF prebiotics modulated the pioglitazone-induced PPARγ activation in a tissue-dependent manner. The co-treatment with ITF prebiotics and pioglitazone maintained the beneficial impact of TZD on glucose homeostasis and adiponectinaemia. Moreover, the combination of both treatments reduced fat mass accumulation, circulating lipids and hepatic triglyceride content, suggesting an overall improvement of metabolism. Finally, the co-treatment favored induction of white-to-brown fat conversion in subcutaneous adipose tissue (SAT), thereby leading to the development of brite adipocytes that could increase the oxidative capacity of the tissue. Conclusions: ITF prebiotics decrease adiposity and improve the metabolic response in HF fed mice treated with TZD.
    Obesity 03/2014; · 3.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Soluble CD163 was suggested as a biomarker of insulin sensitivity and CD163 mRNA expression representing macrophage content in adipose tissue (AT). Objective: The aim of this study was to investigate, in cross-sectional and prospective design, the relationship between sCD163 circulating levels and, CD163 mRNA expression in adipose tissue and insulin sensitivity assessed by euglycemic-hyperinsulinemic clamp. Design, Setting, Participants, and Interventions: Two cohorts of subjects were examined in the study. Cohort 1: forty-two women with wide range of BMI (17-48 kg/m(2)); Cohort 2: twenty-seven obese women, who followed a dietary intervention consisting of 1 month very low-calorie diet, and 5 months of weight-stabilization period. Main Outcome Measures: Serum levels of CD163 and mRNA expression of CD163 and CD68 in subcutaneous and visceral AT were determined, and insulin sensitivity (expressed as glucose disposal rate (GDR)) was measured in Cohort I. In Cohort 2, serum levels of CD163, mRNA expressions of CD163, CD68, and CD163-shedding factors (TACE and TIPM3) in subcutaneous AT were examined and GDR was measured before and during dietary intervention. Results: In Cohort 1, circulating sCD163 correlated with CD163 mRNA levels in both subcutaneous and visceral AT. sCD163 and CD163 mRNA expression in both fat depots correlated with GDR. In Cohort 2, the diet-induced changes of sCD163 levels did not correlate with those of CD163, CD 68, TACE and TIMP3 mRNA levels. Although the pattern of the diet-induced change of sCD163 paralleled that of GDR there was no correlation between the changes of these two variables. Conclusion: sCD163 correlates with CD163 mRNA expression in subcutaneous and visceral AT and with whole-body insulin sensitivity in steady state condition. These associations are not observed in respect to the diet-induced changes during weight-reducing hypocaloric diet.
    The Journal of clinical endocrinology and metabolism 01/2014; · 6.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Weight loss reduces risk factors associated with obesity. However, long-term metabolic improvement remains a challenge. We investigated quantitative gene expression of subcutaneous adipose tissue in obese individuals and its relationship with low calorie diet and long term weight maintenance induced changes in insulin resistance.
    PLoS ONE 01/2014; 9(7):e98707. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Une association inverse entre le contenu en lipides intramyocellulaires et la sensibilité à l’insuline existe chez les sujets sédentaires. Cette relation disparait chez des individus entraînés en endurance et réfère au paradoxe des athlètes. Une dérégulation de l’expression des lipases musculaire pourrait contribuer à l’insulino-résistance. L’objectif de ce travail était d’étudier l’association entre contenu en lipides intramyocellulaires, expression des lipases, capacité oxydative et sensibilité à l’insuline chez des sédentaires, des athlètes et des obèses intolérants au glucose avant et après perte de poids. Matériels et méthodes Nous avons étudié des sujets de poids normal sédentaires et entraînés en endurance, ainsi que des obèses intolérants au glucose avant et après perte de poids induite par un régime hypocalorique. La sensibilité à l’insuline a été évaluée par clamp hyperinsulinémique-euglycémique, les triacylglycérols et diacylglycérols ont été mesurés par chromatographie gazeuse. L’expression des lipases a été étudiée par Western-blot et la capacité oxydative évaluée par mesure de l’activité citrate synthase. Résultats Nos données montrent une forte association entre la sensibilité à l’insuline, la capacité oxydative et l’expression des lipases. Ces trois paramètres sont augmentés chez les athlètes et diminués chez les obèses comparés aux sédentaires. Nous observons une dissociation entre contenu en lipides intramyocellulaires toxiques et sensibilité à l’insuline avec une augmentation du contenu en diacylglycérols à la fois chez l’obèse et chez l’athlète. Nous observons également une diminution nette des triacylglycérols et diacylglycérols et de l’expression des lipases après perte de poids chez les obèses. Ces changements interviennent vis-à-vis d’une amélioration de la sensibilité à l’insuline et sans modification de la capacité oxydative musculaire. Conclusion Ces résultats suggèrent que les lipides intramyocellulaires totaux, l’expression des lipases et la capacité oxydative musculaire ne sont pas systématiquement associés, et ne constituent donc pas de bons marqueurs de la sensibilité à l’insuline.
    Diabetes & Metabolism. 01/2014; 40:A11.
  • [Show abstract] [Hide abstract]
    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.
    Diabetes & Metabolism. 01/2014; 40:A3–A4.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Brite adipocytes are inducible energy-dissipating cells expressing UCP1 which appear within white adipose tissue of healthy adult individuals. Recruitment of these cells represents a potential strategy to fight obesity and associated diseases. Using human Multipotent Adipose-Derived Stem cells, able to convert into brite adipocytes, we show that arachidonic acid strongly inhibits brite adipocyte formation via a cyclooxygenase pathway leading to secretion of PGE2 and PGF2α. Both prostaglandins induce an oscillatory Ca++ signaling coupled to ERK pathway and trigger a decrease in UCP1 expression and in oxygen consumption without altering mitochondriogenesis. In mice fed a standard diet supplemented with ω6 arachidonic acid, PGF2α and PGE2 amounts are increased in subcutaneous white adipose tissue and associated with a decrease in the recruitment of brite adipocytes. Our results suggest that dietary excess of ω6 polyunsaturated fatty acids present in Western diets, may also favor obesity by preventing the “browning” process to take place.
    Molecular Metabolism. 01/2014;
  • [Show abstract] [Hide abstract]
    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.
    Journal of physiology and biochemistry 12/2013; · 1.65 Impact Factor
  • Cedric Moro, Dominique Langin
    Diabetes 12/2013; 62(12):e29. · 7.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ß1-2-adrenergic receptors (AR) are key regulators of cardiac contractility and remodeling in response to catecholamines. ß3-AR expression is enhanced in diseased human myocardium, but its impact on remodeling is unknown. Mice with cardiac myocyte-specific expression of human ß3-AR (ß3-TG) and wild-type (WT) littermates were used to compare myocardial remodeling in response to isoproterenol (Iso) or Angiotensin II (Ang II). ß3-TG and WT had similar morphometric and haemodynamic parameters at baseline. ß3-AR co-localized with caveolin-3, eNOS and nNOS in adult transgenic myocytes, which constitutively produced more cyclic GMP, detected with a new transgenic FRET sensor. Iso and Ang II produced hypertrophy and fibrosis in WT mice, but not in ß3-TG mice, which also had less re-expression of fetal genes and TGF-beta1. Protection from Iso-induced hypertrophy was reversed by non-specific nitric oxide synthase (NOS) inhibition at low dose Iso, and by preferential nNOS inhibition at high dose Iso. Adenoviral overexpression of ß3-AR in isolated cardiac myocytes also increased NO production and attenuated hypertrophy to Iso and phenylephrine (PE). Hypertrophy was restored upon NOS or Protein Kinase G inhibition. Mechanistically, ß3-AR overexpression inhibited PE-induced Nuclear Factor of Activated T-cells (NFAT) activation. Cardiac-specific overexpression of ß3-AR does not affect cardiac morphology at baseline, but inhibits the hypertrophic response to neurohormonal stimulation in vivo and in vitro, through a NOS-mediated mechanism. Activation of the cardiac ß3-AR pathway may provide future therapeutic avenues for the modulation of hypertrophic remodeling.
    Circulation 11/2013; · 15.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represents an adaptive response that preserves WAT lipid homeostasis in obese and insulin resistant states.In our experiments we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance, from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 down-regulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation, facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.
    Diabetes 11/2013; 62(11):3697-3708. · 7.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Accumulation of adipose tissue in lower body lowers risk of cardiovascular and metabolic disorders. The molecular basis of this protective effect of gluteofemoral depot is not clear. The aim of this study was to compare the profile of expression of inflammation-related genes in subcutaneous gluteal (sGAT) and abdominal (sAAT) adipose tissue at baseline and in response to multiphase weight-reducing dietary intervention (DI). 14 premenopausal healthy obese women underwent a 6 months´ DI consisting of 1 month very-low-calorie-diet (VLCD), subsequent 2 months' low-calorie-diet and 3 months' weight maintenance diet (WM). Paired samples of sGAT and sAAT were obtained before and at the end of VLCD and WM periods. mRNA expression of 17 genes (macrophage markers, cytokines) was measured using RT-qPCR on chip-platform. At baseline, there were no differences in gene expression of macrophage markers and cytokines between sGAT and sAAT. The dynamic changes induced by DI were similar in both depots for all genes except for three cytokines (IL6, IL10, CCL2) that differed in their response during weight maintenance phase. The results show that, in obese women, there are no major differences between sGAT and sAAT in expression of inflammation-related genes at baseline conditions and in response to the weight-reducing DI.
    Physiological research / Academia Scientiarum Bohemoslovaca 11/2013; · 1.53 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    The Journal of clinical endocrinology and metabolism 10/2013; · 6.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lysophosphatidic acid (LPA) is a pro-fibrotic mediator acting via specific receptors (LPARs) and is synthesized by autotaxin, which expression is increased in obesity. We tested whether LPA could play a role in adipose tissue (AT)-fibrosis associated with obesity. Fibrosis [type I, III, and IV collagens (COL), fibronectin (FN), TGFβ, CTGF and αSMA] and inflammation (MCP1 and F4/80) markers were quantified: (i) in vivo in inguinal (IAT) and perigonadic (PGAT) AT from obese-diabetic db/db mice treated with the LPAR antagonist Ki16425 (5mg/kg/day ip for 7weeks); and (ii) in vitro in human AT explants in primary culture for 72h in the presence of oleoyl-LPA (10μM) and/or Ki16425 (10μM) and/or the HIF-1α inhibitor YC-1 (100μM). Treatment of db/db mice with Ki16425 reduced COL I and IV mRNAs in IAT and PGAT while COL III mRNAs were only reduced in IAT. This was associated with reduction of COL protein staining in both IAT and PGAT. AT explants showed a spontaneous and time-dependent increase in ATX expression and production of LPA in the culture medium, along with increased levels of COL I and III, TGFβ and αSMA mRNAs and of COL protein staining. In vitro fibrosis was blocked by Ki16425 and was further amplified by oleoyl-LPA. LPA-dependent in vitro fibrosis was blocked by co-treatment with YC1. Our results show that endogenous and exogenous LPA exert a pro-fibrotic activity in AT in vivo and in vitro. This activity could be mediated by an LPA1R-dependent pathway and could involve HIF-1α.
    Biochimica et Biophysica Acta 10/2013; · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the time-course of the expression of key lipolysis-regulating genes in the subcutaneous adipose tissue (SCAT) during different phases of a 6-month dietary intervention. Fifteen obese women (BMI 34.7+/-1.0 kg.m(-2)) underwent a 6-month dietary intervention consisting of 1 month very low calorie diet (VLCD), followed by 2 months low calorie diet (LCD) and 3 months weight maintenance diet (WM). At each phase of the dietary intervention, a needle microbiopsy of the abdominal SCAT was obtained to evaluate mRNA expression of key lipolysis-regulating genes and a hyperinsulinemic euglycemic clamp (HEC) was performed. Dietary intervention induced a body weight reduction of 9.8% and an improvement of insulin sensitivity as assessed by a HEC. Compared to pre-diet levels, mRNA levels of the adrenergic beta(2)-receptor in SCAT were higher at the end of VLCD and not different at the end of LCD and WM. In contrast, the expression of the adrenergic alpha(2)-receptor was lower at the end of VLCD and LCD compared to the pre-diet levels and did not differ at WM. Adipose triglyceride lipase and hormone-sensitive lipase levels were lower than the pre-diet levels at the end of LCD only, while phosphodiesterase-3B and the insulin receptor levels did not change throughout the dietary intervention. The results suggest that the regulation pattern of the genes that are involved in the control of lipolysis is different at the respective phases of the dietary intervention and depends on the duration of the diet and the status of energy balance.
    Physiological research / Academia Scientiarum Bohemoslovaca 09/2013; · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionIt has been suggested that metabolic benefits of physical exercise could be mediated by myokines. We examined here the effect of exercise training on skeletal muscle expression of a panel of myokines in humans. Pathways regulating myokine expression were investigated in human myotubes.Methods Eleven obese non diabetic male subjects were enrolled in an 8-week endurance training program. Insulin sensitivity was assessed by oral glucose tolerance test. Subcutaneous adipose tissue and Vastus Lateralis muscle biopsies were collected before and after training. RNAs were prepared from adipose tissue and skeletal muscle. Primary culture of myoblasts was established.ResultsAs expected, exercise training improved aerobic capacity and decreased fat mass. No significant change in interleukin 6, fibroblast growth factor 21, myostatin or irisin mRNA level was found in muscle after training. A 2-fold increase in apelin mRNA level was found in muscle but not in adipose tissue. No change in circulating myokine and adipokine plasma levels was observed in the resting state in response to training. Interestingly, apelin was significantly expressed and secreted in primary human myotubes. Apelin gene expression was up-regulated by cyclic AMP and calcium unlike the other myokines investigated. Importantly, muscle apelin mRNA levels were positively related to whole-body insulin sensitivity.Conclusion Collectively, our data show that exercise training up-regulates muscle apelin expression in obese subjects. Apelin expression is induced by exercise signalling pathways and secreted in vitro in human primary myotubes, and may behave as a novel exercise-regulated myokine with autocrine/paracrine action.International Journal of Obesity accepted article preview online, 27 August 2013. doi:10.1038/ijo.2013.158.
    International journal of obesity (2005) 08/2013; · 5.22 Impact Factor
  • Pierre-Marie Badin, Dominique Langin, Cedric Moro
    [Show abstract] [Hide abstract]
    ABSTRACT: Intramyocellular triacylglycerol (IMTG) is emerging as an important energy fuel source during muscle contraction and are adaptively increased in response to exercise, without adverse physiological effects. Paradoxically, elevated IMTG content in obese and type 2 diabetics has been linked to insulin resistance, highlighting the importance of IMTG pools in physiology and pathology. Two separate views suggest that IMTG dynamics are determinant for skeletal muscle fat oxidation, and that disruption of IMTG dynamics facilitates the accumulation of lipotoxic intermediates such as diacylglycerols and ceramides that interfere with insulin signaling. Thus, understanding the factors that control IMTG dynamics is crucial. Here we discuss recent literature describing the regulation of IMTG pools with a particular emphasis on lipases and lipid droplet (LD)-associated proteins.
    Trends in Endocrinology and Metabolism 08/2013; · 8.90 Impact Factor

Publication Stats

7k Citations
1,364.89 Total Impact Points

Institutions

  • 1992–2014
    • French Institute of Health and Medical Research
      • Institute of Metabolic and Cardiovascular Diseases I2MC
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Telecommunications for Space and Aeronautics
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2012–2013
    • University of Copenhagen
      • • Faculty of Science
      • • Department of Human Nutrition
      Copenhagen, Capital Region, Denmark
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 2010–2013
    • Bispebjerg Hospital, Copenhagen University
      • Institute of Preventive Medicine
      Copenhagen, Capital Region, Denmark
    • University of Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
    • Hospital Universitari Joan XXIII de Tarragona
      Tarraco, Catalonia, Spain
    • Institut de Recherche en Cancerologie de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 2002–2013
    • University Hospital Brussels
      • Department of Internal Medicine
      Bruxelles, Brussels Capital Region, Belgium
    • University of Antwerp
      Antwerpen, Flanders, Belgium
    • Howard Hughes Medical Institute
      Maryland, United States
  • 1997–2013
    • Charles University in Prague
      • 3rd Faculty of Medicine
      Praha, Praha, Czech Republic
    • Laval University
      • Département de Médecine
      Québec, Quebec, Canada
  • 1989–2013
    • Paul Sabatier University - Toulouse III
      • • Faculté de médecine Purpan
      • • Institut des Maladies Métaboliques et Cardiovasculaires de Toulouse - UMRS 1048 - I2MC
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2011
    • University of Guelph
      Guelph, Ontario, Canada
  • 2002–2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2005–2009
    • Maastricht University
      • Humane Biologie
      Maastricht, Provincie Limburg, Netherlands
    • Hotel Dieu Hospital
      Kingston, Ontario, Canada
  • 2004–2008
    • Karolinska University Hospital
      • Department of Surgery
      Tukholma, Stockholm, Sweden
    • Université de Rennes 2
      Roazhon, Brittany, France
  • 2004–2007
    • Centre Hospitalier Universitaire de Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 1996–2007
    • Karolinska Institutet
      • Institutionen för medicin, Huddinge
      Solna, Stockholm, Sweden
  • 2006
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 1992–2004
    • Lund University
      • Department of Biophysical Chemistry
      Lund, Skåne, Sweden
  • 2003
    • University of Burgundy
      Dijon, Bourgogne, France
  • 1998
    • Institut Louis Bachelier
      Lutetia Parisorum, Île-de-France, France