Equipe 2 : « Régulation of Muscle Mass and Metabolic Disorders »

????????????????????????????????????

CarMeN’ Team 2  gathers scientists and clinicians to work on the determinants of sedentary behaviour and obesity, and on the role of the regulation of muscle mass and metabolism in obesity complications, such as insulin resistance.

We are working on the hypothesis that abnormalities in muscle tissue adaptation to environmental changes (particularly changes in physical activity level) may modulate general metabolic parameters and thus impact health status (development or worsening of obesity, insulin resistance, type 2 diabetes as well as of other factors involved in the development of cardiovascular risk).

We are focusing on the deleterious consequences of sedentary behavior, to decipher the molecular mechanisms and the signalling pathways that link continuous low levels of energy expenditure with alterations of muscle homeostasis.

Our group is focusing on:

  • Identification of the events that link muscle dysfunction and sedentary behavior and affect health (real-life phenotyping, novel imaging methodologies, stable isotope metabolic measurement, micro-biopsies for tissue investigations, genomic and histology analyses)
  • Identification of clinical interventions that may restore muscle mass and homeostasis to counter-balanced negative health outcomes associated with sedentary behavior (models of severe physical inactivity that allow to test different counter-protocoles, physical activity protocols, nutritional interventions, use of drugs, in lean and obese subjects, and in an innovative model of hibernating bear)
  • Identification of the molecular actors involved in muscle dysfunction during sedentary behavior (impact of intracellular lipid accumulation, specific role of SREBP1c and its partners, omic analyses to identify new candidate genes)
  • Characterization of the specific role of extracellular vesicles released from skeletal muscle in muscle physiology and inter-organ cross talks (exosomes, exosomal miRNAs), and use of circulating miRNAs as biomarkers of whole body homeostasis.

Ongoing Research projects

  1. In vivo modulation of physical activity to study muscle homeostasis and metabolic health outcomes

Several exploratory and interventional research studies are already developed or will be programmed, both in humans and animal models, to investigate the impact of altered skeletal muscle adaptation in response to sedentary behavior.

These programs benefit from all the expertise and facilities that have been developed by/or in collaboration with our team (real-life phenotyping, novel imaging methodologies, stable isotope metabolic measurement, micro-biopsies for tissue investigations, genomic and histology facilities), which allow to investigate the consequences of physical activity modulations either at whole body level or at cellular level.

1.a) Projects in humans

1) Medium- and long-term bed-rest based on terrestrial models for the physiological changes experienced in human spaceflight under weightless conditions, or on a well-established model of severe physical inactivity that allow to test different counter-measures (physical activity protocols, nutritional, drugs) (financial support from CNES and ESA, the French and European Spatial Agencies)

2) Free-living cross-sectional and interventional studies aiming at reducing or increasing spontaneous non-exercise physical activity, in various groups of normal subjects with contrasted fat mass phenotypes or of patients (e.g. severe obese, insulin-resistant and diabetic patients).

Bed-Rest Study (ESA AO13-BR CNES 2015-2018).

The European project “Functional and metabolic consequences of ectopic fat storage during bed rest: a mechanistic and kinetic approach” is dedicated to the exploration of long-term effects of the bed-rest, and to test the prevention of the deleterious effects associated with the sedentary behaviour by using dietary cocktails of natural products containing anti-oxidant and anti-inflammatory properties. In this project, our team is responsible for clinical experiment coordination and supervision (C. Simon) and for tissue molecular analysis (E. Lefai).

Briefly two groups of subjects will be submitted to a 60-day bed-rest, in energy balance conditions, either without or with daily dietary mixture. Similar explorations will be performed before bed-rest, after 10 days of bed-rest and after 60 days of bed-rest (energetic and metabolic exploration at whole body level and molecular and biochemical exploration of tissue samples from muscle, blood, fat, and possibly liver).

This project would allow us to delineate the mechanisms and temporal sequence of events by which severe and prolonged sedentary behaviour in humans lead to ectopic fat storage and insulin resistance. We will also determine if and how a dietary mixture of natural products with reported anti-oxidant and anti-inflammatory properties will limit the deleterious impact of bed rest.

STIMOB (PHRC 2015-2018).

This multi-centric project conducted in collaboration with the University hospitals of Grenoble and St-Etienne (France), is an innovative approach in the fight against sedentary behavior. We are testing the impact of muscle electric stimulations in severe inactive obese patients. The hypothesis is that muscle electro-stimulations will have a benefic impact on muscle mass and structure and on its metabolism. By restoring muscle function and exercise peripheral tolerance, we are hypothesizing that it will favor higher spontaneous muscle activity and thus will lead to reduce the bad side effects of whole body metabolic alterations and the cardiovascular risk associated with inactivity. Briefly two randomized groups of patients (placebo vs electro-stimulated) will be studied during two years.

 Projects under development: Besides these ongoing studies, we are preparing future international partnerships (Dr S. Blanc, IPHC Strasbourg; Pr D O’Gorman University of Dublin and M Aubertin, Kinesiology Department, University of Montreal) to study the impact of increasing/disrupting sedentary time, in real life conditions.

1.b) Projects in animals

 oursHibernatus. Hibernating bear has developed specific adaptations to maintain its skeletal muscle mass tissue ours 2during extended periods of disuse and starvation, (e.g.; hibernation), two conditions that are known to trigger immediate and massive muscle atrophy in humans and laboratory rodent models. The bear’s ability to maintain its muscle functionality contrasts dramatically with classical model demonstrating a general loss of skeletal muscle mass and strength in response to inactivity.

Within a collaborative European program, our team is focusing on the identification of specific compounds in winter bear serum, able to positively regulate muscle homeostasis. For this purpose, serum from bears collected in summer (non-hibernating) or in winter (hibernating) will be tested for their ability to modify the protein balance, the metabolism and the phenotype of cultured muscle cells

figure equipe 2

 

 

We have already demonstrated that, compared to summer, winter bear serum has the ability to modify gene expressions and phosphorylation of several key factors involved in protein synthesis and degradation, thus increasing cell protein content and triggering hypertrophy of human myotubes.

The identification of new biological markers involved in the bad side effects of inactivity should pave the way for identification of novel therapeutic targets and bioactive compounds that will be used to prevent muscle alterations in sedentary behavior or in disuse situations.

 

 

  1. Functional characterization of candidate moleculars actors

With our current human and animal studies aiming at modulating sedentary behavior, we have already identified several candidate genes.

2.a) Role of SREBP-1

We have recently identified and characterized the dual role of the SREBP-1 transcription factor in skeletal muscle, which both negatively regulates muscle mass in addition to positively regulate cellular lipid synthesis.

We and others have already demonstrated that SREBP-1 muscle nuclear content is affected by nutritional status or exercise. Indeed, SREBP-1 activity is known to dramatically vary, depending on fasted and fed states, as the active form of SREBP-1 increases in postprandial periods to promote intracellular lipid synthesis. We therefore hypothesize that in sedentary and/or obese patients, the lack of a normal modulation of SREBP-1 activity may contribute to muscle phenotype alterations, affecting both metabolism and muscle mass.

We therefore aim at further characterizing the molecular mechanisms and the signaling pathways that control SREBP-1 nuclear accumulation, interplaying with energy metabolism, contractile activity and substrate oxidation in skeletal muscle. We will also focus on protein-protein interactions, looking at partners that can hold back SREBP-1 into the nucleus and thus maintain its activity. In muscle, lamin appears to be a very promising candidate, being already described as an interacting partner of SREBP-1, and for which genetic mutations have strong consequences on muscle mass but also on lipid distribution.

 

Apart from SREBP-1, other relevant candidates that will be identified in ongoing protocols will be studied thanks to in vitro models that we have developed, especially the in vitro culture of differentiated myotubes (from human and rodent). Specific gene expressions can be experimentally modified thanks to our expertise in recombinant adenovirus engineering or by using RNA silencing. In parallel, thanks to our DIOMEDE human tissue collection (2013-2018), we are collecting liver, muscle, blood, visceral and subcutaneous adipose tissue samples from lean, obese and DT2 patients. This valuable and unique biobank allows us to prepare conditioned media and primary cells that can be use to validate our hypothesis or to identify novel candidate genes. Additionally, in collaboration with our Swiss partners (2015-2018 financial support by FNS grant), we are exploring the lipidomic profile of skeletal muscle biopsies and cells from insulin-sensitive, insulin-resistant and sedentary volonteers, from the DIOMEDE collection.

2.b) Role of extracellular miRNAs cross-talks between skeletal muscle and the other insulin-senitive tissues (S. Rome)

MicroRNAs (miRNAs) are a class of evolutionary conserved non-coding RNAs of 19-22 nucleotides that function as neEquipe 2_fig 3 (png)gative modulators of gene expression, regulating fundamental cellular processes in diverse organisms, including the control of fat metabolism, adipocyte differentiation, energy homeostasis, glucose-stimulated insulin secretion and inflammation. Our works on the mechanisms of insulin-resistance during T2DM and obesity has identified altered insulin response of miR-1 and miR-133a, two muscle-specific miRNAs controlling muscle mass and homeostasis under the control of SREBP-1c (Granjon, Diabetes 2009). In this context, we are now interesting in understanding the role of miRNAs in skeletal muscle physiology with a specific focus on miRNAs released from muscle cells via the exosomal route. We are postulated that they would be involved in the development of metabolic complications associated with sedentary behavior and insulin-resistance, associated with skeletal muscle cell dysfunctions, and would be involved in the cross-talk between muscle and the other insulin-sensitive tissues.

 

fig equipe 2 sophie

2.c) Use of extracellular miRNAs as biomarkers of whole body homeostasis (S. Rome)

It has become clear that sedentary behaviour and obesity have multiple known, and likely unknown, physiological impacts which are not easily addressed by single-gene, protein or metabolite approaches. Therefore, a combination of all genomic-based data may be necessary to detect the full metabolic consequences of sedentary behavior and associated diseases, or to monitor the impact of lifestyle interventions. Circulating miRNAs may represent such a new class of integrative biomarker. A growing number of studies have demonstrated that circulating miRNA levels are good biomarkers for cancers, neurological disorders and metabolic diseases and thus we want to test whether circulating miRNAs might reflect either the early phases of metabolic stress or the development of metabolic syndrome associated with physical inactivity.

2017

  1. Benoit B, Meugnier E, Castelli M, Chanon S, Vieille-Marchiset A, Durand C, Bendridi N, Pesenti S, Monternier PA, Durieux AC, Freyssenet D, Rieusset J, Lefai E, Vidal H, Ruzzin J. (2017) Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. Nat Med 23; 990-996

2. Blond E, Disse E, Cuerq C, Drai J, Valette PJ, Laville M, Thivolet C, Simon C, Caussy C.(2017) EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease in severely obese people: do they lead to over-referral? Diabetologia 60; 1218-1222

3. Condello, G., Puggina, A., Aleksovska, K., Buck, C., Burns, C., Cardon, G., Carlin, A., Simon, C., Ciarapica, D., Coppinger, T., Cortis, C., D’Haese, S., De Craemer, M., Di Blasio, A., Hansen, S., Iacoviello, L., Issartel, J., Izzicupo, P., Jaeschke, L., Kanning, M., Kennedy, A., Ling, F. C. M., Luzak, A., Napolitano, G., Nazare, J. A., Perchoux, C., Pesce, C., Pischon, T., Polito, A., Sannella, A., Schulz, H., Sohun, R., Steinbrecher, A., Schlicht, W., Ricciardi, W., MacDonncha, C., Capranica, L., Boccia, S. and Consortium, D. (2017) Behavioral determinants of physical activity across the life course: a « DEterminants of DIet and Physical ACtivity » (DEDIPAC) umbrella systematic literature review. International Journal of Behavioral Nutrition and Physical Activity. 14; 234.

4. Dupuis, M., Kuczewski, E., Villeneuve, L., Bin-Dorel, S., Haine, M., Falandry, C., Gilbert, T., Passot, G., Glehen, O. and Bonnefoy, M. (2017) Age Nutrition Chirurgie (ANC) study: impact of a geriatric intervention on the screening and management of undernutrition in elderly patients operated on for colon cancer, a stepped wedge controlled trial. Bmc Geriatrics. 17; 9.

5. Hess, F., Salze, P., Weber, C., Feuillet, T., Charreire, H., Menai, M., Perchoux, C., Nazare, J. A., Simon, C., Oppert, J. M. and Enaux, C. (2017) Active Mobility and Environment: A Pilot Qualitative Study for the Design of a New Questionnaire. Plos One. 12; 15.

6. Lefai E, Blanc S, Momken I, Antoun E, Chery I, Zahariev A, Gabert L, Bergouignan A, Simon C. (2017) Exercise training improves fat metabolism independent of total energy expenditure in sedentary overweight men, but does not restore lean metabolic phenotype. Int J Obes (Lond)

7. Ru P, Hu P, Geng F, Mo X, Cheng C, Yoo JY, Cheng X, Wu X, Guo JY, Nakano I, Lefai E, Kaur B, Chakravarti A, Guo D.(2017) Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth.  Cell Rep   18; 1076

 

2016

  1. Aswad, H., Jalabert, A. and Rome, S. (2016) Depleting extracellular vesicles from fetal bovine serum alters proliferation and differentiation of skeletal muscle cells in vitro BMC Biotechnology 16 32
  1. Bongard, V., Arveiler, D., Dallongeville, J., Ruidavets, J. B., Wagner, A., Simon, C., Marecaux, N. and Ferrieres, J. (2016) Food groups associated with a reduced risk of 15-year all-cause death European Journal of Clinical Nutrition 70 715-22
  1. Bonnefoy, M., Berrut, G. and Gilbert, T. (2016) Prevention of impaired mobility in the elderly in primary care: a brief report Gériatrie et Psychologie Neuropsychiatrie du Vieillissement 14 16-22
  1. Cassel, R., Ducreux, S., Alam, M. R., Dingreville, F., Berle, C., Burda-Jacob, K., Chauvin, M. A., Chikh, K., Paita, L., Al-Mawla, R., Crola Da Silva, C., Rieusset, J., Thivolet, C., Van Coppenolle, F. and Madec, A. M. (2016) Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon PLoS One 11 e0148686
  1. Caussy, C., Charriere, S., Meirhaeghe, A., Dallongeville, J., Lefai, E., Rome, S., Cuerq, C., Euthine, V., Delay, M., Marmontel, O., Di Filippo, M., Lagarde, M., Moulin, P. and Marcais, C. (2016) Multiple microRNA regulation of lipoprotein lipase gene abolished by 3’UTR polymorphisms in a triglyceride-lowering haplotype harboring p.Ser474Ter Atherosclerosis 246 280-6
  1. Condello G, Ling FC, Bianco A, Chastin S, Cardon G, Ciarapica D, Conte D, Cortis C, De Craemer M, Di Blasio A, Gjaka M, Hansen S, Holdsworth M, Iacoviello L, Izzicupo P, Jaeschke L, Leone L, Manoni L, Menescardi C, Migliaccio S, Nazare JA, Perchoux C, Pesce C, Pierik F, Pischon T, Polito A, Puggina A, Sannella A, Schlicht W, Schulz H, Simon C, Steinbrecher A, MacDonncha C, Capranica L; DEDIPAC consortium.. Using concept mapping in the development of the EU-PAD framework (EUropean-Physical Activity Determinants across the life course): a DEDIPAC-study. BMC Public Health. 2016 Nov 9;16(1):1145.
  1. De Arcangelis, V., Strimpakos, G., Gabanella, F., Corbi, N., Luvisetto, S., Magrelli, A., Onori, A., Passananti, C., Pisani, C., Rome, S., Severini, C., Naro, F., Mattei, E., Di Certo, M. G. and Monaco, L. (2016) Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy Journal of Cellular Physiology 231 224-32
  1. Gastebois, C., Chanon, S., Rome, S., Durand, C., Pelascini, E., Jalabert, A., Euthine, V., Pialoux, V., Blanc, S., Simon, C. and Lefai, E. (2016) Transition from physical activity to inactivity increases skeletal muscle miR-148b content and triggers insulin resistance Physiological Reports 4 17 e12902
  1. Gastebois, C., Villars, C., Drai, J., Canet-Soulas, E., Blanc, S., Bergouignan, A., Lefai, E. and Simon, C. (2016) Effects of training and detraining on adiponectin plasma concentration and muscle sensitivity in lean and overweight men European Journal of Applied Physiology 116 2135-2144
  1. Geng, F., Cheng, X., Wu, X., Yoo, J. Y., Cheng, C., Guo, J. Y., Mo, X., Ru, P., Hurwitz, B., Kim, S. H., Otero, J., Puduvalli, V., Lefai, E., Ma, J., Nakano, I., Horbinski, C., Kaur, B., Chakravarti, A. and Guo, D. (2016) Inhibition of SOAT1 Suppresses Glioblastoma Growth via Blocking SREBP-1-Mediated Lipogenesis Clinical Cancer Research 22 5337-5348
  1. Jalabert, A., Vial, G., Guay, C., Wiklander, O. P., Nordin, J. Z., Aswad, H., Forterre, A., Meugnier, E., Pesenti, S., Regazzi, R., Danty-Berger, E., Ducreux, S., Vidal, H., El-Andaloussi, S., Rieusset, J. and Rome, S. (2016) Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice Diabetologia 59 1049-58
  1. Liminet, C., Vouillarmet, J., Chikh, K. and Disse, E. (2016) Antibody-Mediated Insulin Resistance: When Insulin and Insulin Receptor Act as Autoantigens in Humans Canadian Journal of Diabetes 40 462-465
  1. Marchand, L., Jalabert, A., Meugnier, E., Van den Hende, K., Fabien, N., Nicolino, M., Madec, A. M., Thivolet, C. and Rome, S. (2016) miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes Journal of Diabetes Research doi.org/10.1155/2016/1869082
  1. Mensah, K., Maire, A., Oppert, J. M., Dugas, J., Charreire, H., Weber, C., Simon, C. and Nazare, J. A. (2016) Assessment of sedentary behaviors and transport-related activities by questionnaire: a validation study BMC Public Health 16 753
  1. Nozieres, C., Chardon, L., Goichot, B., Borson-Chazot, F., Hervieu, V., Chikh, K., Lombard-Bohas, C. and Walter, T. (2016) Neuroendocrine tumors producing calcitonin: characteristics, prognosis and potential interest of calcitonin monitoring during follow-up European Journal of Endocrinology 174 335-41
  1. Occelli, P., Touzet, S., Rabilloud, M., Ganne, C., Poupon Bourdy, S., Galamand, B., Debray, M., Dartiguepeyrou, A., Chuzeville, M., Comte, B., Turkie, B., Tardy, M., Luiggi, J. S., Jacquet-Francillon, T., Gilbert, T. and Bonnefoy, M. (2016) Impact of a transition nurse program on the prevention of thirty-day hospital readmissions of elderly patients discharged from short-stay units: study protocol of the PROUST stepped-wedge cluster randomised trial BMC Geriatrics 16 57
  1. O’Donoghue, G., Perchoux, C., Mensah, K., Lakerveld, J., van der Ploeg, H., Bernaards, C., Chastin, S. F., Simon, C., O’Gorman, D., Nazare, J. A. and consortium, D. (2016) A systematic review of correlates of sedentary behaviour in adults aged 18-65 years: a socio-ecological approach BMC Public Health 16 163
  1. Rouveure, A. C., Bonnefoy, M. and Laville, M. (2016) Conservative treatment, hemodialysis or peritoneal dialysis for elderly patients: The choice of treatment does not influence the survival Néphrologie & Thérapeutique 12 32-7
  1. Ru, P., Hu, P., Geng, F., Mo, X., Cheng, C., Yoo, J. Y., Cheng, X., Wu, X., Guo, J. Y., Nakano, I., Lefai, E., Kaur, B., Chakravarti, A. and Guo, D. (2016) Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth Physiological Reports 16 1527-35

 

2015

1. Bastian, T., Maire, A., Dugas, J., Ataya, A., Villars, C., Gris, F., Perrin, E., Caritu, Y., Doron, M., Blanc, S., Jallon, P., and Simon, C. (2015) Automatic identification of physical activity types and sedentary behaviors from triaxial accelerometer: laboratory-based calibrations are not enough. Journal of applied physiology. 118, 716-722

2. Bonnefoy, M., Berrut, G., Lesourd, B., Ferry, M., Gilbert, T., Guerin, O., Hanon, O., Jeandel, C., Paillaud, E., Raynaud-Simon, A., Ruault, G., and Rolland, Y. (2015) Frailty and nutrition: searching for evidence. The journal of nutrition, health & aging. 19, 250-257

3. Cheng, C., Ru, P., Geng, F., Liu, J., Yoo, J. Y., Wu, X., Cheng, X., Euthine, V., Hu, P., Guo, J. Y., Lefai, E., Kaur, B., Nohturfft, A., Ma, J., Chakravarti, A., and Guo, D. (2015) Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth. Cancer Cell. 28, 569-581

4. Cuerq, C., Peretti, N., Chikh, K., Mialon, A., Guillaumont, M., Drai, J., and Blond, E. (2015) Overview of the in vitro stability of commonly measured vitamins and carotenoids in whole blood. Annals of Clinical Biochemistry. 52, 259-269

5. Eljaafari, A., Robert, M., Chehimi, M., Chanon, S., Durand, C., Vial, G., Bendridi, N., Madec, A. M., Disse, E., Laville, M., Rieusset, J., Lefai, E., Vidal, H., and Pirola, L. (2015) Adipose Tissue-Derived Stem Cells From Obese Subjects Contribute to Inflammation and Reduced Insulin Response in Adipocytes Through Differential Regulation of the Th1/Th17 Balance and Monocyte Activation. Diabetes. 64, 2477-2488

6. Feuillet, T., Charreire, H., Menai, M., Salze, P., Simon, C., Dugas, J., Hercberg, S., Andreeva, V. A., Enaux, C., Weber, C., and Oppert, J. M. (2015) Spatial heterogeneity of the relationships between environmental characteristics and active commuting: towards a locally varying social ecological model. International journal of health geographics. 14, 12

7. Gilbert, T., Chidiac, C., Bonnefoy, M., and Ferry, T. (2015) Tuberculosis of the cavum revealed by acute facial pain. BMJ case reports. 2015,

8. Guay, C., Menoud, V., Rome, S., and Regazzi, R. (2015) Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells. Cell communication and signaling. 13, 17

9. Honnorat, D., Disse, E., Millot, L., Mathiotte, E., Claret, M., Charrie, A., Drai, J., Garnier, L., Maurice, C., Durand, E., Simon, C., Dupuis, O., and Thivolet, C. (2015) Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes? Diabetes & Metabolism. 41, 393-400

10. Menai, M., Charreire, H., Feuillet, T., Salze, P., Weber, C., Enaux, C., Andreeva, V. A., Hercberg, S., Nazare, J. A., Perchoux, C., Simon, C., and Oppert, J. M. (2015) Walking and cycling for commuting, leisure and errands: relations with individual characteristics and leisure-time physical activity in a cross-sectional survey (the ACTI-Cites project). The international journal of behavioral nutrition and physical activity. 12, 150

11. Perrin, L., Loizides-Mangold, U., Skarupelova, S., Pulimeno, P., Chanon, S., Robert, M., Bouzakri, K., Modoux, C., Roux-Lombard, P., Vidal, H., Lefai, E., and Dibner, C. (2015) Human skeletal myotubes display a cell-autonomous circadian clock implicated in basal myokine secretion. Molecular metabolism. 4, 834-845

12. Prabu, P., Rome, S., Sathishkumar, C., Aravind, S., Mahalingam, B., Shanthirani, C. S., Gastebois, C., Villard, A., Mohan, V., and Balasubramanyam, M. (2015) Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes. PLoS One. 10, e0128372

13. Revel, F., Gilbert, T., Roche, S., Drai, J., Blond, E., Ecochard, R., and Bonnefoy, M. (2015) Influence of oxidative stress biomarkers on cognitive decline. Journal of Alzheimer’s disease. 45, 553-560

14. Rome, S. (2015) Use of miRNAs in biofluids as biomarkers in dietary and lifestyle intervention studies. Genes & nutrition. 10, 483

15. Rouveure, A. C., Bonnefoy, M., and Laville, M. (2016) [Conservative treatment, hemodialysis or peritoneal dialysis for elderly patients: The choice of treatment does not influence the survival]. Nephrologie & therapeutique. 12, 32-37

16. Rudwill, F., Bergouignan, A., Gastebois, C., Gauquelin-Koch, G., Lefai, E., Blanc, S., and Simon, C. (2015) Effect of enforced physical inactivity induced by 60-day of bed rest on hepatic markers of NAFLD in healthy normal-weight women. Liver international. 35, 1700-1706

17. Saidj, M., Menai, M., Charreire, H., Weber, C., Enaux, C., Aadahl, M., Kesse-Guyot, E., Hercberg, S., Simon, C., and Oppert, J. M. (2015) Descriptive study of sedentary behaviours in 35,444 French working adults: cross-sectional findings from the ACTI-Cites study. BMC public health. 15, 379

18. Scherdel, P., Botton, J., Rolland-Cachera, M. F., Leger, J., Pele, F., Ancel, P. Y., Simon, C., Castetbon, K., Salanave, B., Thibault, H., Lioret, S., Peneau, S., Gusto, G., Charles, M. A., and Heude, B. (2015) Should the WHO growth charts be used in France? PLoS One. 10, e0120806

19. Scridon, A., Fouilloux-Meugnier, E., Loizon, E., Rome, S., Julien, C., Barres, C., and Chevalier, P. (2015) Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias. European pacing, arrhythmias, and cardiac electrophysiology. 17, 160-165

2014

1. Aswad H, Forterre A, Wiklander OP, Vial G, Danty-Berger E, Jalabert A, Lamazière A, Meugnier E, Pesenti S, Ott C, Chikh K, El-Andaloussi S, Vidal H, Lefai E, Rieusset J and Rome S. Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice. Diabetologia. 2014 Oct;57(10):2155-64.

2. Caussy, C., Charriere, S., Marcais, C., Di Filippo, M., Sassolas, A., Delay, M., Euthine, V., Jalabert, A., Lefai, E., Rome, S., and Moulin, P. (2014) An APOA5 3′ UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site. American journal of human genetics. 94, 129-134

3. Chaix, B., Simon, C., Charreire, H., Thomas, F., Kestens, Y., Karusisi, N., Vallee, J., Oppert, J. M., Weber, C., and Pannier, B. (2014) The environmental correlates of overall and neighborhood based recreational walking (a cross-sectional analysis of the RECORD Study). The international journal of behavioral nutrition and physical activity. 11, 20

4. Forterre, A., Jalabert, A., Chikh, K., Pesenti, S., Euthine, V., Granjon, A., Errazuriz, E., Lefai, E., Vidal, H., and Rome, S. (2014) Myotube-derived exosomal miRNAs downregulate Sirtuin1 in myoblasts during muscle cell differentiation. Cell Cycle. 13, 78-89

5. Giovannelli, J., Dallongeville, J., Wagner, A., Bongard, V., Laillet, B., Marecaux, N., Ruidavets, J. B., Haas, B., Ferrieres, J., Arveiler, D., Simon, C., and Dauchet, L. (2014) Validation of a short, qualitative food frequency questionnaire in French adults participating in the MONA LISA-NUT study 2005-2007. Journal of the Academy of Nutrition and Dietetics. 114, 552-561

6. Kellou, N., Sandalinas, F., Copin, N., and Simon, C. (2014) Prevention of unhealthy weight in children by promoting physical activity using a socio-ecological approach: What can we learn from intervention studies? Diabetes & metabolism.

7. Ortega, F. J., Mercader, J. M., Moreno-Navarrete, J. M., Rovira, O., Guerra, E., Esteve, E., Xifra, G., Martinez, C., Ricart, W., Rieusset, J., Rome, S., Karczewska-Kupczewska, M., Straczkowski, M., and Fernandez-Real, J. M. (2014) Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes care. 37, 1375-1383

8. Scridon, A., Fouilloux-Meugnier, E., Loizon, E., Rome, S., Julien, C., Barres, C., and Chevalier, P. (2014) Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

9. Simon, C., Kellou, N., Dugas, J., Platat, C., Copin, N., Schweitzer, B., Hausser, F., Bergouignan, A., Lefai, E., and Blanc, S. (2014) A socio-ecological approach promoting physical activity and limiting sedentary behavior in adolescence showed weight benefits maintained 2.5 years after intervention cessation. Int J Obes (Lond).

2013

1. Agin, A., Charrie, A., Chikh, K., Tabarin, A., and Vezzosi, D. (2013) Fast test: clinical practice and interpretation. Annales d’endocrinologie. 74, 174-184

2. Amigues, I., Schott, A. M., Amine, M., Gelas-Dore, B., Veerabudun, K., Paillaud, E., Beauchet, O., Rolland, Y., Canoui Poitrine, F., and Bonnefoy, M. (2013) Low skeletal muscle mass and risk of functional decline in elderly community-dwelling women: the prospective EPIDOS study. Journal of the American Medical Directors Association. 14, 352-357

3. Annane, D., Timsit, J. F., Megarbane, B., Martin, C., Misset, B., Mourvillier, B., Siami, S., Chagnon, J. L., Constantin, J. M., Petitpas, F., Souweine, B., Amathieu, R., Forceville, X., Charpentier, C., Tesniere, A., Chastre, J., Bohe, J., Colin, G., Cariou, A., Renault, A., Brun-Buisson, C., and Bellissant, E. (2013) Recombinant human activated protein C for adults with septic shock: a randomized controlled trial. American journal of respiratory and critical care medicine. 187, 1091-1097

4. Bergouignan, A., Antoun, E., Momken, I., Schoeller, D. A., Gauquelin-Koch, G., Simon, C., and Blanc, S. (2013) Effect of contrasted levels of habitual physical activity on metabolic flexibility. J Appl Physiol (1985). 114, 371-379

5. Bergouignan, A., Momken, I., Lefai, E., Antoun, E., Schoeller, D. A., Platat, C., Chery, I., Zahariev, A., Vidal, H., Gabert, L., Normand, S., Freyssenet, D., Laville, M., Simon, C., and Blanc, S. (2013) Activity energy expenditure is a major determinant of dietary fat oxidation and trafficking, but the deleterious effect of detraining is more marked than the beneficial effect of training at current recommendations. The American journal of clinical nutrition. 98, 648-658

6. Berthoux, E., Dufour, C., Raharisondraibe, E., and Bonnefoy, M. (2013) Preventable drug events in acute geriatric unit. Geriatrie et psychologie neuropsychiatrie du vieillissement. 11, 15-20

7. Briolay, A., Jaafar, R., Nemoz, G., and Bessueille, L. (2013) Myogenic differentiation and lipid-raft composition of L6 skeletal muscle cells are modulated by PUFAs. Biochimica et biophysica acta. 1828, 602-613

8. Carobbio, S., Hagen, R. M., Lelliott, C. J., Slawik, M., Medina-Gomez, G., Tan, C. Y., Sicard, A., Atherton, H. J., Barbarroja, N., Bjursell, M., Bohlooly, Y. M., Virtue, S., Tuthill, A., Lefai, E., Laville, M., Wu, T., Considine, R. V., Vidal, H., Langin, D., Oresic, M., Tinahones, F. J., Fernandez-Real, J. M., Griffin, J. L., Sethi, J. K., Lopez, M., and Vidal-Puig, A. (2013) Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity. Diabetes. 62, 3697-3708

9. Doron, M., Bastian, T., Maire, A., Dugas, J., Perrin, E., Gris, F., Guillemaud, R., Deschamps, T., Bianchi, P., Caritu, Y., Simon, C., and Jallon, P. (2013) Estimation of physical activity monitored during the day-to-day life by an autonomous wearable device (SVELTE project). Conference proceedings : … Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2013, 4629-4632

10. Falandry, C., Brain, E., Bonnefoy, M., Mefti, F., Jovenin, N., Rigal, O., Guillem, O., El Kouri, C., Uwer, L., Abadie-Lacourtoisie, S., Cretin, J., Jacquin, J. P., Paraiso, D., and Freyer, G. (2013) Impact of geriatric risk factors on pegylated liposomal doxorubicin tolerance and efficacy in elderly metastatic breast cancer patients: final results of the DOGMES multicentre GINECO trial. Eur J Cancer. 49, 2806-2814

11. Forterre, A., Jalabert, A., Chikh, K., Pesenti, S., Euthine, V., Granjon, A., Errazuriz, E., Lefai, E., Vidal, H., and Rome, S. (2013) Myotube-derived exosomal miRNAs downregulate Sirtuin1 in myoblasts during muscle cell differentiation. Cell Cycle. 13

12. Jaafar, R., De Larichaudy, J., Chanon, S., Euthine, V., Durand, C., Naro, F., Bertolino, P., Vidal, H., Lefai, E., and Nemoz, G. (2013) Phospholipase D regulates the size of skeletal muscle cells through the activation of mTOR signaling. Cell communication and signaling : CCS. 11, 55

13. Jamilloux, Y., Bonnefoy, M., Valeyre, D., Varron, L., Broussolle, C., and Seve, P. (2013) Elderly-onset sarcoidosis: prevalence, clinical course, and treatment. Drugs & aging. 30, 969-978

14. Kai, S. H., Bongard, V., Simon, C., Ruidavets, J. B., Arveiler, D., Dallongeville, J., Wagner, A., Amouyel, P., and Ferrieres, J. (2013) Low-fat and high-fat dairy products are differently related to blood lipids and cardiovascular risk score. European journal of preventive cardiology.

15. Le, J., Dallongeville, J., Wagner, A., Arveiler, D., Haas, B., Cottel, D., Simon, C., and Dauchet, L. (2013) Attitudes toward healthy eating: a mediator of the educational level-diet relationship. European journal of clinical nutrition. 67, 808-814

16. Luquain-Costaz, C., Lefai, E., Arnal-Levron, M., Markina, D., Sakai, S., Euthine, V., Makino, A., Guichardant, M., Yamashita, S., Kobayashi, T., Lagarde, M., Moulin, P., and Delton-Vandenbroucke, I. (2013) Bis(monoacylglycero)phosphate accumulation in macrophages induces intracellular cholesterol redistribution, attenuates liver-X receptor/ATP-Binding cassette transporter A1/ATP-binding cassette transporter G1 pathway, and impairs cholesterol efflux. Arteriosclerosis, thrombosis, and vascular biology. 33, 1803-1811

17. Madec, A. M., Cassel, R., Dubois, S., Ducreux, S., Vial, G., Chauvin, M. A., Mesnier, A., Chikh, K., Bosco, D., Rieusset, J., Van Coppenolle, F., and Thivolet, C. (2013) Losartan, an angiotensin II type 1 receptor blocker, protects human islets from glucotoxicity through the phospholipase C pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 27, 5122-5130

18. Ng, Y. H., Rome, S., Jalabert, A., Forterre, A., Singh, H., Hincks, C. L., and Salamonsen, L. A. (2013) Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation. PloS one. 8, e58502

19. Robert, M., Ferrand-Gaillard, C., Disse, E., Espalieu, P., Simon, C., Laville, M., Gouillat, C., and Thivolet, C. (2013) Predictive factors of type 2 diabetes remission 1 year after bariatric surgery: impact of surgical techniques. Obesity surgery. 23, 770-775

20. Rolland, Y., de Souto Barreto, P., Abellan Van Kan, G., Annweiler, C., Beauchet, O., Bischoff-Ferrari, H., Berrut, G., Blain, H., Bonnefoy, M., Cesari, M., Duque, G., Ferry, M., Guerin, O., Hanon, O., Lesourd, B., Morley, J., Raynaud-Simon, A., Ruault, G., Souberbielle, J. C., and Vellas, B. (2013) Vitamin D supplementation in older adults: searching for specific guidelines in nursing homes. The journal of nutrition, health & aging. 17, 402-412

21. Rome, S. (2013) Are extracellular microRNAs involved in type 2 diabetes and related pathologies? Clinical biochemistry. 46, 937-945

22. Rouffet, D., Villars, C., Fissoune, R., Sappey-Marinier, D., Laville, M., Ibarrola, D., Sothier, M., Monnet, M. F., Ovize, M., Bonnefoy, M., Boesch, C., and Canet-Soulas, E. (2013) Intramyocellular lipid variations in active older men: relationship with aerobic fitness. Acta Physiol (Oxf). 207, 516-523

23. Rudwill, F., Blanc, S., Gauquelin-Koch, G., Chouker, A., Heer, M., Simon, C., and Bergouignan, A. (2013) Effects of different levels of physical inactivity on plasma visfatin in healthy normal-weight men. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 38, 689-693

24. Timsit, J. F., Bouadma, L., Mimoz, O., Parienti, J. J., Garrouste-Orgeas, M., Alfandari, S., Plantefeve, G., Bronchard, R., Troche, G., Gauzit, R., Antona, M., Canet, E., Bohe, J., Herrault, M. C., Schwebel, C., Ruckly, S., Souweine, B., and Lucet, J. C. (2013) Jugular versus femoral short-term catheterization and risk of infection in intensive care unit patients. Causal analysis of two randomized trials. American journal of respiratory and critical care medicine. 188, 1232-1239

25. Wei, K., Piecewicz, S. M., McGinnis, L. M., Taniguchi, C. M., Wiegand, S. J., Anderson, K., Chan, C. W., Mulligan, K. X., Kuo, D., Yuan, J., Vallon, M., Morton, L. C., Lefai, E., Simon, M. C., Maher, J. J., Mithieux, G., Rajas, F., Annes, J. P., McGuinness, O. P., Thurston, G., Giaccia, A. J., and Kuo, C. J. (2013) A liver Hif-2alpha-Irs2 pathway sensitizes hepatic insulin signaling and is modulated by Vegf inhibition. Nature medicine. 19, 1331-1337