137 results on '"Gauquelin-Koch, G"'
Search Results
2. Concurrent BMP signaling maintenance and TGF-β signaling inhibition is a hallmark of natural resistance to muscle atrophy
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Cussonneau, L, Boyer, B, Meugnier, E, Gauquelin-Koch, G, Arnemo, J, Lefai, E, Bertile, F, Combaret, L., and INRAE, Université Clermont Auvergne
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[SDV]Life Sciences [q-bio] ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] - Abstract
National audience; Muscle atrophy arises from a multiplicity of physiological or pathological situations (e.g. diabetes, cancers, aging, physical inactivity…) and its consequences are very detrimental at whole-body level. Even though knowledge of the underlying mechanisms keeps growing, there is still no proven treatment to date. To address this major clinical challenge, we selected here an innovative approach that compares muscle adaptations between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of disuse-induced atrophy in mouse. Remarkably, the bear has the unique ability to withstand muscle loss during hibernation, being able to cope with main triggers of atrophy, physical inactivity and prolonged fasting. Using transcriptomic analysis by RNA sequencing, we identified 2693 differentially expressed genes between the active versus hibernating period in bear muscle. We focused on TGF-β and BMP signaling pathways that are respectively involved in muscle mass loss and maintenance. During hibernation, gene expression of the TGF-β and BMP pathways components was overall downregulated and upregulated, respectively. On the contrary, an increased expression of TGF-β signaling genes and a decreased expression of BMP signaling genes was observed in mice muscles during unloading. We have further substantiated this opposite regulation between atrophied muscles of the unloaded mouse and non-atrophied muscles of the hibernating bear at the protein level. Altogether, our data identified a balance between TGF-β and BMP signaling pathways as crucial for muscle mass maintenance during long-term physical inactivity. In addition to the TGF-β pathway, already targeted in a wide range of therapies, the BMP pathway therefore appears to be an additional potential therapeutic target to prevent muscle atrophy.
- Published
- 2021
3. Hormonal changes during long-term isolation
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Custaud, M. A., de Chantemele, E. Belin, Larina, I. M., Nichiporuk, I. A., Grigoriev, A., Duvareille, M., Gharib, C., and Gauquelin-Koch, G.
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- 2004
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4. Regional blood flow in conscious rats after head-down suspension
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Somody, L., Fagette, S., Blanc, S., Frutoso, J., Gharib, C., and Gauquelin-Koch, G.
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- 1998
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5. Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest
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Pavy-Le Traon, A., Vasseur, P., Sigaudo, D., Maillet, A., Fortrat, J. O., Hughson, R. L., Gauquelin-Koch, G., and Gharib, C.
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- 1997
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6. Metabolic reprogramming involving glycolysis in the hibernating brown bear skeletal muscle
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Chazarin, B. (Blandine), Storey, K. (Kenneth B.), Ziemianin, A. (Anna), Chanon, S. (Stéphanie), Plumel, M. (Marine), Chery, I. (Isabelle), Durand, C. (Christine), Evans, A.L. (Alina L.), Arnemo, J.M. (Jon M.), Zedrosser, A. (Andreas), Swenson, J.E. (Jon E.), Gauquelin-Koch, G. (Guillemette), Simon, C. (Chantal), Blanc, S. (Stephane), Lefai, E. (Etienne), Bertile, F. (Fabrice), Chazarin, B. (Blandine), Storey, K. (Kenneth B.), Ziemianin, A. (Anna), Chanon, S. (Stéphanie), Plumel, M. (Marine), Chery, I. (Isabelle), Durand, C. (Christine), Evans, A.L. (Alina L.), Arnemo, J.M. (Jon M.), Zedrosser, A. (Andreas), Swenson, J.E. (Jon E.), Gauquelin-Koch, G. (Guillemette), Simon, C. (Chantal), Blanc, S. (Stephane), Lefai, E. (Etienne), and Bertile, F. (Fabrice)
- Abstract
Background: In mammals, the hibernating state is characterized by biochemical adjustments, which include metabolic rate depression and a shift in the primary fuel oxidized from carbohydrates to lipids. A number of studies of hibernating species report an upregulation of the levels and/or activity of lipid oxidizing enzymes in muscles during torpor, with a concomitant downregulation for glycolytic enzymes. However, other studies provide contrasting data about the regulation of fuel utilization in skeletal muscles during hibernation. Bears hibernate with only moderate hypothermia but with a drop in metabolic rate down to ~ 25% of basal metabolism. To gain insights into how fuel metabolism is regulated in hibernating bear skeletal muscles, we examined the vastus lateralis proteome and other changes elicited in brown bears during hibernation. Results: We show that bear muscle metabolic reorganization is in line with a suppression of ATP turnover. Regulation of muscle enzyme expression and activity, as well as of circulating metabolite profiles, highlighted a preference for lipid substrates during hibernation, although the data suggested that muscular lipid oxidation levels decreased due to metabolic rate depression. Our data also supported maintenance of muscle glycolysis that could be fuelled from liver gluconeogenesis and mobilization of muscle glycogen stores. During hibernation, our data also suggest that carbohydrate metabolism in bear muscle, as well as protein sparing, could be controlled, in part, by actions of n-3 polyunsaturated fatty acids like docosahexaenoic acid. Conclusions: Our work shows that molecular mechanisms in hibernating bear skeletal muscle, which appear consistent with a hypometabolic state, likely contribute to energy and protein savings. Maintenance of glycolysis could help to sustain muscle functionality for situations such as an unexpected exit from hibernation that would require a rapid increase in ATP production for muscle contraction. Th
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- 2019
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7. Endocrine responses to 7 days of head-down bed rest and orthostatic tests in men and women
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Millet, C., Custaud, M.-A., Maillet, A., Allevard, A.-M., Duvareille, M., Gauquelin-Koch, G., Gharib, C., and Fortrat, J.-O.
- Published
- 2001
8. Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men
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Millet, C, Custaud, M. A, Allevard, A. M, Zaouali-Ajina, M, Monk, T. H, Arnaud, S. B, Gharib, C, and Gauquelin-Koch, G
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Aerospace Medicine - Abstract
Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).
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- 2001
9. Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation
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Millet, C, Custaud, M. A, Allevard, A. M, Zaouali-Ajina, M, Monk, T. H, Arnaud, S. B, Claustrat, B, Gharib, C, and Gauquelin-Koch, G
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Aerospace Medicine - Abstract
We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na+ and K+) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P < 0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal.24 h(-1) to 2,450 (36) kcal.24 h(-1), where 1 kcal.h(-1) = 1.163 J.s(-1); P< 0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K+ excretion was unchanged during HDBR, whereas for Na+ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na+ rhythm and abolition of the aldosterone rhythm.
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- 2001
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10. Metabolic inflexibility is an early marker of bed-rest–induced glucose intolerance even when fat mass is stable
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Rudwill, F, O'Gorman, D, Lefai, E, Chery, I, Zahariev, A, Normand, S, Pagano, AF, Chopard, A, Damiot, A, Laurens, C, Hodson, L, Canet-Soulas, E, Heer, M, Meuthen, PF, Buehlmeier, J, Baecker, N, Meiller, Laure, Gauquelin-Koch, G, Blanc, S, Simon, C, Bergouignan, A, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Diabete Consortium 3U, Dublin City University, National Institute for Cellular Biotechnology, Dublin City University [Dublin] (DCU), School of Health and Human Performance, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Nutrition Research Center, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford [Oxford], Institute of Human Nutrition and Food Science, Rheinische Friedrich-Wilhelms-Universität Bonn, Aerospace Medical Institute, German Aerospace Center (DLR), Department of Child and Adolescent Psychiatry (UMCU), UMCU, Centre National d'Études Spatiales [Toulouse] (CNES), Division of Diabetes, Endocrinology and Metabolism, Department of Physics [Boulder], University of Colorado [Boulder]-University of Colorado [Boulder], European Space Agency (ESA), Centre National de la Recherche Scientifique, European (ESA) space agency, CNES, French (CNES) space agency, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)
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Adult ,Male ,Time Factors ,Diabetes, Pancreatic and Gastrointestinal Hormones ,Medizin ,Glucose Intolerance ,Humans ,Longitudinal Studies ,résistance à l'insuline ,Clinical Research Articles ,Adiposity ,flexibilité ,Cross-Over Studies ,fat mass ,masse grasse ,muscle squelettique ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,pliability ,Diet ,diabète type 2 ,Early Diagnosis ,voluntary muscle ,Adipose Tissue ,Body Composition ,Insulin Resistance ,Energy Metabolism ,Bed Rest ,Biomarkers - Abstract
Context The effects of energy-balanced bed rest on metabolic flexibility have not been thoroughly examined. Objective We investigated the effects of 21 days of bed rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We hypothesized that protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy. Design and Setting Randomized crossover longitudinal study conducted at the German Aerospace Center, Cologne, Germany. Participants and Interventions Ten healthy men were randomly assigned to dietary countermeasure or isocaloric control diet during a 21-day bed rest. Outcome Measures Before and at the end of the bed rest, metabolic flexibility was assessed during a meal test. Secondary outcomes were glucose tolerance by oral glucose tolerance test, body composition by dual energy X-ray absorptiometry, ectopic fat storage by magnetic resonance imaging, and inflammation and oxidative stress markers. Results Bed rest decreased the ability to switch from fat to carbohydrate oxidation when transitioning from fasted to fed states (i.e., metabolic inflexibility), antioxidant capacity, fat-free mass (FFM), and muscle insulin sensitivity along with greater fat deposition in muscle (P < 0.05 for all). Changes in fasting insulin and inflammation were not observed. However, glucose tolerance was reduced during acute overfeeding. Protein supplementation did not prevent FFM loss and metabolic alterations. Conclusions Physical inactivity triggers metabolic inflexibility, even when energy balance is maintained. Although reduced insulin sensitivity and increased fat deposition were observed at the muscle level, systemic glucose intolerance was detected only in response to a moderately high-fat meal. This finding supports the role of physical inactivity in metabolic inflexibility and suggests that metabolic inflexibility precedes systemic glucose intolerance., Bed-rest–induced physical inactivity triggers metabolic inflexibility, which can be used as an early marker of metabolic disturbances developed in response to the adoption of sedentary behaviors.
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- 2018
11. Proteolysis inhibition by hibernating bear serum leads to increased protein content in human muscle cells
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Chanon, S. (Stéphanie), Chazarin, B. (Blandine), Toubhans, B. (Benoit), Durand, C. (Christine), Chery, I. (Isabelle), Robert, M. (Maud), Vieille-Marchiset, A. (Aurélie), Swenson, J.E. (Jon E.), Zedrosser, A. (Andreas), Evans, A.L. (Alina L.), Brunberg, S. (Sven), Arnemo, J.M. (Jon M.), Gauquelin-Koch, G. (Guillemette), Storey, K. (Kenneth B.), Simon, C. (Chantal), Blanc, S. (Stéphane), Bertile, F. (Fabrice), Lefai, E. (Etienne), Chanon, S. (Stéphanie), Chazarin, B. (Blandine), Toubhans, B. (Benoit), Durand, C. (Christine), Chery, I. (Isabelle), Robert, M. (Maud), Vieille-Marchiset, A. (Aurélie), Swenson, J.E. (Jon E.), Zedrosser, A. (Andreas), Evans, A.L. (Alina L.), Brunberg, S. (Sven), Arnemo, J.M. (Jon M.), Gauquelin-Koch, G. (Guillemette), Storey, K. (Kenneth B.), Simon, C. (Chantal), Blanc, S. (Stéphane), Bertile, F. (Fabrice), and Lefai, E. (Etienne)
- Abstract
Muscle atrophy is one of the main characteristics of human ageing and physical inactivity, with resulting adverse health outcomes. To date, there are still no efficient therapeutic strategies for its prevention and/or treatment. However, during hibernation, bears exhibit a unique ability for preserving muscle in conditions where muscle atrophy would be expected in humans. Therefore, our objective was to determine whether there are components of bear serum which can control protein balance in human muscles. In this study, we exposed cultured human differentiated muscle cells to bear serum collected during winter and summer periods, and measured the impact on cell protein content and turnover. In addition, we explored the signalling pathways that control rates of protein synthesis and degradation. We show that the protein turnover of human myotubes is reduced when incubated with winter bear serum, with a dramatic inhibition of proteolysis involving both proteasomal and lysosomal systems, and resulting in an increase in muscle cell protein content. By modulating intracellular signalling pathways and inducing a protein sparing phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders.
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- 2018
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12. Effect of a 14-day hindlimb suspension on β-adrenoreceptors in rats
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Bouzeghrane, F, Somody, L, Gallo-Bona, N, Gauquelin-Koch, G, Gharib, C, and Fagette, S
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- 1999
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13. Pain and Vertebral Dysfunction in Dry Immersion: A Model of Microgravity Simulation Different from Bed Rest Studies
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Treffel, L., primary, Massabuau, N., additional, Zuj, K., additional, Custaud, M.-A., additional, Gauquelin-Koch, G., additional, Blanc, S., additional, Gharib, C., additional, and Millet, C., additional
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- 2017
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14. The cardiovascular effects of salidroside in the Goto-Kakizaki diabetic rat model
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Alameddine, A, Fajloun, Z, Bourreau, Jennifer, Gauquelin-Koch, G, Yuan, M, Gauguier, D, Derbré, Séverine, Ayer, Audrey, Custaud, Marc-Antoine, Navasiolava, N, Substances d'Origine Naturelle et Analogues Structuraux (SONAS), Université d'Angers (UA), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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[SDV]Life Sciences [q-bio] - Abstract
International audience; Many factors, including hyperglycemia, hypertension, obesity, dyslipidemia, and a sedentary lifestyle, contribute to a high prevalence of cardiovascular disease. Specific vascular impairment treatments in the context of diabetes and vascular risk need to be improved. Salidroside is the primary active component of Rhodiola rosea and has documented antioxidative, cardioprotective, and vasculoprotective properties. The aim of this study was to test the hypothesis that salidroside has protective effects against hyperglycemia, hypertension, and vasodilation impairment in the Goto-Kakizaki (GK) rat model of diabetes. We evaluated cardiovascular parameters (e.g., daytime/nighttime systolic and diastolic blood pressure, heart rate, and activity), metabolic parameters (e.g., body weight, food and water consumption, serum fructosamine level, glucose tolerance), eNOS / phospho-eNOS expression level and in vitro vascular reactivity of aorta and second-order mesenteric arteries in Wistar-Kyoto (control) and GK (diabetic) rats treated with salidroside (40 mg/kg) or placebo (water) for 5 weeks. GK rats showed hypertension, marked glucose intolerance, and impaired endothelium-dependent and endothelium-independent vasodilation capacity. Salidroside showed beneficial effects on endothelial and non-endothelial vasodilation and likely acts on the endothelium and smooth muscle cells through the soluble guanylyl cyclase pathway. Despite its vascular effects, salidroside had no effect on blood pressure and heart rate in GK and control rats, it did not improve glucose metabolism or limit hypertension in the GK model of type 2 diabetes.
- Published
- 2015
15. NT-ProBNP levels, water and sodium homeostasis in healthy men: effects of 7 days of dry immersion
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Navasiolava, N., Pajot, P., Gallois, Y., Pastushkova, L., Kulchitsky, V., Gauquelin-Koch, G., Kozlovskaya, I., Heer, M., Hand, O., Larina, I., and Custaud, M.
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water immersion - Published
- 2011
16. Does resistance exercise prevent body fluid changes after a 90-day bed rest ?
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BELIN DE CHANTEMLE, E, Blanc, S, Pellet, N, Duvareille, M, Ferretti, Guido, GAUQUELIN KOCH, G, and Gharib, C. AND CUSTAUD M. A.
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Cardiovascular system ,Space science ,Humans - Published
- 2004
17. Cardiovascular deconditioning: From autonomic nervous system to microvascular dysfunctions
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Coupé, M., primary, Fortrat, J.O., additional, Larina, I., additional, Gauquelin-Koch, G., additional, Gharib, C., additional, and Custaud, M.A., additional
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- 2009
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18. Cardiac Natriuretic Peptide Response to Water Restriction in the Hormonal Adaptation of Two Semidesert Rodents from West Africa (Steatomys caurinus, Taterillus gracilis)
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Lacas, S, primary, Allevard, A.M, additional, Ag'Atteinine, S, additional, Gallo-Bona, N, additional, Gauquelin-Koch, G, additional, Hardin-Pouzet, H, additional, Gharib, C, additional, Sicard, B, additional, and Maurel, D, additional
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- 2000
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19. Effects of Acute and Chronic Starvation on Central and Peripheral Noradrenaline Turnover, Blood Pressure and Heart Rate in the Rat
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El Fazaa, S., primary, Somody, L., additional, Gharbi, N., additional, Kamoun, A., additional, Gharib, C., additional, and Gauquelin-koch, G., additional
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- 1999
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20. Adaptations to a 7-day head-down bed rest with thigh cuffs.
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Millet C, Custaud M, Allevard A, Gharib C, Gauquelin-Koch G, and Fortrat J
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- 2000
21. Effects of Acute and Chronic Starvation on Central and Peripheral Noradrenaline Turnover, Blood Pressure and Heart Rate in the Rat
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Fazaa, S., Somody, L., Gharbi, N., Kamoun, A., Gharib, C., and Gauquelin‐koch, G.
- Abstract
When faced with stress, an organism calls upon several mechanisms to maintain biological homeostasis. The cardiovascular system is the first to respond usually with an increase in arterial pressure and tachycardia. Therefore we investigated the central and peripheral sympathetic responses to acute and chronic starvation in Wistar rats. The noradrenaline (NA) turnover rate was determined in different catecholaminergic nuclei (A1, A2, A5, A6) as well as the arterial blood pressure and heart rate modifications. During acute starvation (3 days of starvation), the NA turnover was increased in the A1 and rostral A2 nuclei as well as in ventricles and kidneys and decreased in the A6 nucleus. During chronic starvation (4 consecutive cycles of 3 days of starvation plus 1 day of feeding), the NA turnover was increased in the A5 and caudal A2 nuclei as well as in ventricles and atria and decreased in the A1 nucleus and kidneys. The arterial blood pressure revealed a gradual decrease during the first 3 days of fasting but the heart rate was not modified. We conclude that starvation should be considered as an unusual state of stress because of the absence of locus coeruleus response (A6 nucleus) despite its well‐defined role in stress reactions. One of the manifestations of these central and peripheral noradrenergic changes is the change in blood pressure during the starvation‐feeding cycles.
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- 1999
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22. Presence of artrial natriuretic peptide in two desert rodents: comparison with rat
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Lacas, S., Bentchikou, M., Gabrion, J., Gallo-Bona, N., Gauquelin-Koch, G., Gharib, C., and Allevard, A.-M.
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- 1998
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23. Skin microcirculatory dysfunction induced by 7 days of dry immersion
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Navasiolava, N. M., Tsvirkun, D. V., Pastushkova, L. Kh, Larina, I. M., Igor Dobrokhotov, Fortrat, J. O., Gharib, G., Gauquelin-Koch, G., and Custaud, M. -A
24. Hormonal changes during a 20-week confinement
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Maillet A, Jens Titze, Gushin V, Nichiporuk I, Ka, Kirsch, Gharib C, and Gauquelin-Koch G
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Male ,Time Factors ,Vasopressins ,Blood Pressure ,Arginine ,Body Mass Index ,Catecholamines ,Heart Rate ,Renin ,Humans ,Energy Intake ,Aldosterone ,Fluid Shifts ,Ecological Systems, Closed ,Space Simulation - Abstract
When the European Space Agency planned the EUROMIR'95 long-duration flight with a European astronaut on board the Russian orbital MIR station, it organized simultaneously a ground simulation, called the Human Behaviour Study, of this manned space mission. The ground simulation was a confinement experiment, and this paper describes the changes in volume-regulating hormones that occurred during and after 20 weeks of confinement.In a normobaric diving chamber, 3 subjects were confined for 135 d. Arterial pressure, plasma concentrations of blood volume-regulating hormones (active renin and arginine-vasopressin), and urinary variables (aldosterone, arginine-vasopressin, and metabolites of catecholamines) were measured before, during, and after confinement.Arterial pressure was increased from week 1 until week 15 of confinement, while heart rate was elevated from week 6 until the end of the simulation. Plasma active renin was elevated throughout the confinement (after week 6). Urine volume increased transitively on the first 2 d of confinement.The results obtained during this long-term confinement experiment have major importance regarding concerns about spaceflight and bed rest data, because we observed hormonal changes during the experiment that normally are assigned to the fluid shift that occurs in weightlessness or in the head-down tilt position (i.e., an increase of renin, an increase of urinary volume during the first two days, and a decreased urinary cyclic guanosine monophosphate.
25. Dry immersion rapidly disturbs iron metabolism in men and women: results from the VIVALDI studies.
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Horeau M, Navasiolava N, Van Ombergen A, Custaud MA, Robin A, Ropert M, Antunes I, Bareille MP, Billette De Villemeur R, Gauquelin-Koch G, Derbré F, and Loréal O
- Abstract
Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity., (© 2024. The Author(s).)
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- 2024
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26. Substrate metabolism in male astronauts onboard the International Space Station: the ENERGY study.
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Le Roux E, Zahariev A, Chery I, Schoeller DA, Bourdier P, Maillet A, Thevenot C, Garnotel M, Gauquelin-Koch G, Van Den Berghe L, Blanc S, Simon C, and Bergouignan A
- Abstract
Bedrest shifts fasting and postprandial fuel selection towards carbohydrate use over lipids, potentially affecting astronauts' performance and health. We investigated whether this change occurs in astronauts after at least 3 months onboard the International Space Station (ISS). We further explored the associations with diet, physical activity (PA), and body composition. Before and during spaceflight, respiratory quotient (RQ), carbohydrate, and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 males (age = 45.7 [SD 7.7] years, BMI = 24.3 [2.1] kg m
- ²). Postprandial substrate use was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). Food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and PA by accelerometry and diary logs. Spaceflight increased fasting RQ (P = 0.01) and carbohydrate oxidation (P = 0.04) and decreased fasting lipid oxidation (P < 0.01). An increase in FQ (P < 0.001) indicated dietary modifications onboard the ISS. Spaceflight-induced RQ changes adjusted for ground RQ correlated with inflight FQ (P < 0.01). In postprandial conditions, nutrient oxidation and ΔRQ were unaffected on average. Lipid oxidation changes negatively correlated with FFM changes and inflight aerobic exercise and positively with FM changes. The opposite was observed for carbohydrate oxidation. ΔRQ changes were negatively and positively related to FM and FFM changes, respectively. In conclusion, fasting substrate oxidation shift observed during spaceflight may primarily result from dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight PA., (© 2024. The Author(s).)- Published
- 2024
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27. Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation.
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Robin A, Van Ombergen A, Laurens C, Bergouignan A, Vico L, Linossier MT, Pavy-Le Traon A, Kermorgant M, Chopard A, Py G, Green DA, Tipton M, Choukér A, Denise P, Normand H, Blanc S, Simon C, Rosnet E, Larcher F, Fernandez P, de Glisezinski I, Larrouy D, Harant-Farrugia I, Antunes I, Gauquelin-Koch G, Bareille MP, Billette De Villemeur R, Custaud MA, and Navasiolava N
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- Humans, Female, Cardiovascular Deconditioning physiology, Immersion, Weightlessness Simulation, Space Flight, Weightlessness adverse effects
- Abstract
Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures., (© 2023. Springer Nature Limited.)
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- 2023
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28. Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target.
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Baranowski RW, Braun JL, Hockey BL, Yumol JL, Geromella MS, Watson CJF, Kurgan N, Messner HN, Whitley KC, MacNeil AJ, Gauquelin-Koch G, Bertile F, Gittings W, Vandenboom R, Ward WE, and Fajardo VA
- Abstract
We examined the effects of ∼30 days of spaceflight on glycogen synthase kinase 3 (GSK3) content and inhibitory serine phosphorylation in murine muscle and bone samples from four separate missions (BION-M1, rodent research [RR]1, RR9, and RR18). Spaceflight reduced GSK3β content across all missions, whereas its serine phosphorylation was elevated with RR18 and BION-M1. The reduction in GSK3β was linked to the reduction in type IIA fibers commonly observed with spaceflight as these fibers are particularly enriched with GSK3. We then tested the effects of inhibiting GSK3 before this fiber type shift, and we demonstrate that muscle-specific Gsk3 knockdown increased muscle mass, preserved muscle strength, and promoted the oxidative fiber type with Earth-based hindlimb unloading. In bone, GSK3 activation was enhanced after spaceflight; and strikingly, muscle-specific Gsk3 deletion increased bone mineral density in response to hindlimb unloading. Thus, future studies should test the effects of GSK3 inhibition during spaceflight., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)
- Published
- 2023
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29. Induction of ATF4-Regulated Atrogenes Is Uncoupled from Muscle Atrophy during Disuse in Halofuginone-Treated Mice and in Hibernating Brown Bears.
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Cussonneau L, Coudy-Gandilhon C, Deval C, Chaouki G, Djelloul-Mazouz M, Delorme Y, Hermet J, Gauquelin-Koch G, Polge C, Taillandier D, Averous J, Bruhat A, Jousse C, Papet I, Bertile F, Lefai E, Fafournoux P, Maurin AC, and Combaret L
- Subjects
- Animals, Mice, Muscle, Skeletal metabolism, Signal Transduction, Transforming Growth Factor beta genetics, Transforming Growth Factor beta metabolism, Hibernation, Activating Transcription Factor 4 genetics, Activating Transcription Factor 4 metabolism, Muscular Atrophy metabolism, Ursidae
- Abstract
Activating transcription factor 4 (ATF4) is involved in muscle atrophy through the overexpression of some atrogenes. However, it also controls the transcription of genes involved in muscle homeostasis maintenance. Here, we explored the effect of ATF4 activation by the pharmacological molecule halofuginone during hindlimb suspension (HS)-induced muscle atrophy. Firstly, we reported that periodic activation of ATF4-regulated atrogenes ( Gadd45a , Cdkn1a , and Eif4ebp1 ) by halofuginone was not associated with muscle atrophy in healthy mice. Secondly, halofuginone-treated mice even showed reduced atrophy during HS, although the induction of the ATF4 pathway was identical to that in untreated HS mice. We further showed that halofuginone inhibited transforming growth factor-β (TGF-β) signalling, while promoting bone morphogenetic protein (BMP) signalling in healthy mice and slightly preserved protein synthesis during HS. Finally, ATF4-regulated atrogenes were also induced in the atrophy-resistant muscles of hibernating brown bears, in which we previously also reported concurrent TGF-β inhibition and BMP activation. Overall, we show that ATF4-induced atrogenes can be uncoupled from muscle atrophy. In addition, our data also indicate that halofuginone can control the TGF-β/BMP balance towards muscle mass maintenance. Whether halofuginone-induced BMP signalling can counteract the effect of ATF4-induced atrogenes needs to be further investigated and may open a new avenue to fight muscle atrophy. Finally, our study opens the way for further studies to identify well-tolerated chemical compounds in humans that are able to fine-tune the TGF-β/BMP balance and could be used to preserve muscle mass during catabolic situations.
- Published
- 2022
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30. Effect of Exercise on Energy Expenditure and Body Composition in Astronauts Onboard the International Space Station: Considerations for Interplanetary Travel.
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Bourdier P, Zahariev A, Schoeller DA, Chery I, Le Roux E, Thevenot C, Maillet A, Garnotel M, Gauquelin-Koch G, Bergouignan A, Blanc S, and Simon C
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- Humans, Energy Metabolism, Exercise, Astronauts, Body Composition
- Abstract
Objective: Body mass (BM) loss and body composition (BC) changes threaten astronauts' health and mission success. However, the energetic contribution of the exercise countermeasure to these changes has never been investigated during long-term missions. We studied energy balance and BC in astronauts during 6-month missions onboard the International Space Station., Methods: Before and after at least 3 months in space, BM, BC, total and activity energy expenditure (TEE and AEE) were measured using the doubly labeled water method in 11 astronauts (2011-2017). Physical activity (PA) was assessed by the SensewearPro® activity-device., Results: Three-month spaceflight decreased BM (- 1.20 kg [SE 0.5]; P = 0.04), mainly due to non-significant fat-free mass loss (FFM; - 0.94 kg [0.59]). The decrease in walking time (- 63.2 min/day [11.5]; P < 0.001) from preflight was compensated by increases in non-ambulatory activities (+ 64.8 min/day [18.8]; P < 0.01). Average TEE was unaffected but a large interindividual variability was noted. Astronauts were stratified into those who maintained (stable_TEE; n = 6) and those who decreased (decreased_TEE; n = 5) TEE and AEE compared to preflight data. Although both groups lost similar BM, FFM was maintained and FM reduced in stable_TEE astronauts, while FFM decreased and FM increased in decreased_TEE astronauts (estimated between-group-difference (EGD) in ΔFFMindex [FFMI] 0.87 kg/m
2 , 95% CI + 0.32 to + 1.41; P = 0.01, ΔFMindex [FMI] - 1.09 kg/m2 , 95% CI - 2.06 to - 0.11 kg/m2 ; P = 0.03). The stable_TEE group had higher baseline FFMI, and greater baseline and inflight vigorous PA than the decreased_TEE group (P < 0.05 for all). ΔFMI and ΔFFMI were respectively negatively and positively associated with both ΔTEE and ΔAEE., Conclusion: Both ground fitness and inflight overall PA are associated with spaceflight-induced TEE and BC changes and thus energy requirements. New instruments are needed to measure real-time individual changes in inflight energy balance components., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)- Published
- 2022
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31. Spinal changes after 5-day dry immersion as shown by magnetic resonance imaging (DI-5-CUFFS).
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Robin A, Navasiolava N, Gauquelin-Koch G, Gharib C, Custaud MA, and Treffel L
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- Back Pain pathology, Humans, Lumbar Vertebrae pathology, Lumbosacral Region pathology, Lumbosacral Region physiology, Magnetic Resonance Imaging methods, Male, Immersion, Intervertebral Disc diagnostic imaging
- Abstract
Astronauts frequently report microgravity-induced back pain, which is generally more pronounced in the beginning of a spaceflight. The dry immersion (DI) model reproduces the early effects of microgravity in terms of global support unloading and fluid shift, both of which are involved in back pain pathogenesis. Here, we assessed spinal changes induced by exposure to 5 days of strict DI in 18 healthy men (25-43-yr old) with ( n = 9) or without ( n = 9) thigh cuffs countermeasure. Intervertebral disk (IVD) height, spinal cord position, and apparent diffusion coefficient (ADC; reflecting global water motion) were measured using magnetic resonance imaging before and after DI. After DI, IVD height increased in thoracic (+3.3 ± 0.8 mm; C
7 -T12 ) and lumbar (+4.5 ± 0.4 mm; T12 -L5 ) regions but not in the cervical region (C2 -C7 ) of the spine. An increase in ADC after DI was observed at the L1 (∼6% increase, from 3.2 to 3.4 × 10-3 mm2 /s; P < 0.001) and L2 (∼3% increase, from 3.4 to 3.5 × 10-3 mm2 /s; P = 0.005) levels. There was no effect of thigh cuffs on spinal parameters. This change in IVD after DI follows the same "gradient" pattern of height increase from the cervical to the lumbar region as observed after bed rest and spaceflight. The increase in ADC at L1 level positively correlated with reported back pain. These findings emphasize the utility of the DI model for studying early spinal changes observed in microgravity.- Published
- 2022
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32. Running vs. resistance exercise to counteract deconditioning induced by 90-day head-down bedrest.
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Robin A, Wang L, Custaud MA, Liu J, Yuan M, Li Z, Lloret JC, Liu S, Dai X, Zhang J, Lv K, Li W, Gauquelin-Koch G, Wang H, Li K, Li X, Qu L, Navasiolava N, and Li Y
- Abstract
Spaceflight is associated with enhanced inactivity, resulting in muscular and cardiovascular deconditioning. Although physical exercise is commonly used as a countermeasure, separate applications of running and resistive exercise modalities have never been directly compared during long-term bedrest. This study aimed to compare the effectiveness of two exercise countermeasure programs, running and resistance training, applied separately, for counteracting cardiovascular deconditioning induced by 90-day head-down bedrest (HDBR). Maximal oxygen uptake ( V ˙ O
2 max), orthostatic tolerance, continuous ECG and blood pressure (BP), body composition, and leg circumferences were measured in the control group (CON: n = 8), running exercise group (RUN: n = 7), and resistive exercise group (RES: n = 7). After HDBR, the decrease in V ˙ O2 max was prevented by RUN countermeasure and limited by RES countermeasure (-26% in CON p < 0.05, -15% in RES p < 0.05, and -4% in RUN ns ). Subjects demonstrated surprisingly modest orthostatic tolerance decrease for different groups, including controls. Lean mass loss was limited by RES and RUN protocols (-10% in CON vs. -5% to 6% in RES and RUN). Both countermeasures prevented the loss in thigh circumference (-7% in CON p < 0.05, -2% in RES ns , and -0.6% in RUN ns ) and limited loss in calf circumference (-10% in CON vs. -7% in RES vs. -5% in RUN). Day-night variations in systolic BP were preserved during HDBR. Decrease in V ˙ O2 max positively correlated with decrease in thigh ( r = 0.54 and p = 0.009) and calf ( r = 0.52 and p = 0.012) circumferences. During this 90-day strict HDBR, running exercise successfully preserved V ˙ O2 max, and resistance exercise limited its decline. Both countermeasures limited loss in global lean mass and leg circumferences. The V ˙ O2 max reduction seems to be conditioned more by muscular than by cardiovascular parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Robin, Wang, Custaud, Liu, Yuan, Li, Lloret, Liu, Dai, Zhang, Lv, Li, Gauquelin-Koch, Wang, Li, Li, Qu, Navasiolava and Li.)- Published
- 2022
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33. DI-5-Cuffs: Bone Remodelling and Associated Metabolism Markers in Humans After Five Days of Dry Immersion to Simulate Microgravity.
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Linossier MT, Peurière L, Fernandez P, Normand M, Beck A, Bareille MP, Bonneau C, Gauquelin-Koch G, and Vico L
- Abstract
Background: The dry immersion (DI) model closely reproduces factors of spaceflight environment such as supportlessness, mechanical and axial unloading, physical inactivity, and induces early increased bone resorption activity and metabolic responses as well as fluid centralization. The main goal of this experiment was to assess the efficacity of venoconstrictive thigh cuffs, as countermeasure to limit cephalad fluidshift, on DI-induced deconditioning, in particular for body fluids and related ophthalmological disorders. Our specific goal was to deepen our knowledge on the DI effects on the musculoskeletal events and to test whether intermittent counteracting fluid transfer would affect DI-induced bone modifications. Methods: Eighteen males divided into Control (DI) or Cuffs (DI-TC) group underwent an unloading condition for 5 days. DI-TC group wore thigh cuffs 8-10 h/day during DI period. Key markers of bone turnover, phospho-calcic metabolism and associated metabolic factors were measured. Results: In the DI group, bone resorption increased as shown by higher level in Tartrate-resistant acid phosphatase isoform 5b at DI
24h . C-terminal telopeptide levels were unchanged. Bone formation and mineralization were also affected at DI24h with a decreased in collagen type I synthesis and an increased bone-specific alkaline phosphatase. In addition, osteocalcin and periostin levels decreased at DI120h . Calcemia increased up to a peak at DI48h , inducing a trend to decrease in parathyroid hormone levels at DI120h . Phosphatemia remained unchanged. Insulin-like growth factor 1 and visfatin were very sensitive to DI conditions as evidenced by higher levels by 120% vs. baseline for visfatin at DI48h . Lipocalin-2, a potential regulator of bone homeostasis, and irisin were unchanged. The changes in bone turnover markers were similar in the two groups. Only periostin and visfatin changes were, at least partially, prevented by thigh cuffs. Conclusion: This study confirmed the rapid dissociation between bone formation and resorption under DI conditions. It revealed an adaptation peak at DI48h , then the maintenance of this new metabolic state during all DI. Notably, collagen synthesis and mineralisation markers evolved asynchronously. Thigh cuffs did not prevent significantly the DI-induced deleterious effects on bone cellular activities and/or energy metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Linossier, Peurière, Fernandez, Normand, Beck, Bareille, Bonneau, Gauquelin-Koch and Vico.)- Published
- 2022
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34. Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations.
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Laurens C, Grundler F, Damiot A, Chery I, Le Maho AL, Zahariev A, Le Maho Y, Bergouignan A, Gauquelin-Koch G, Simon C, Blanc S, and Wilhelmi de Toledo F
- Subjects
- Adult, Exercise, Humans, Male, Middle Aged, Muscles, Prospective Studies, Adaptation, Physiological, Fasting
- Abstract
Background: Fasting is attracting an increasing interest as a potential strategy for managing diseases, including metabolic disorders and complementary cancer therapy. Despite concerns of clinicians regarding protein catabolism and muscle loss, evidence-based clinical data in response to long-term fasting in healthy humans are scarce. The objective of this study was to measure clinical constants, metabolic, and muscular response in healthy men during and after a 10 day fast combined with a physical activity programme., Methods: Sixteen men (44 ± 14 years; 26.2 ± 0.9 kg/m
2 ) fasted with a supplement of 200-250 kcal/day and up to 3 h daily low-intensity physical activity according to the peer-reviewed Buchinger Wilhelmi protocol. Changes in body weight (BW) and composition, basal metabolic rate (BMR), physical activity, muscle strength and function, protein utilization, inflammatory, and metabolic status were assessed during the 10 day fast, the 4 days of food reintroduction, and at 3 month follow-up., Results: The 10 day fast decreased BW by 7% (-5.9 ± 0.2 kg, P < 0.001) and BMR by 12% (P < 0.01). Fat mass and lean soft tissues (LST) accounted for about 40% and 60% of weight loss, respectively, -2.3 ± 0.18 kg and -3.53 ± 0.13 kg, P < 0.001. LST loss was explained by the reduction in extracellular water (44%), muscle and liver glycogen and associated water (14%), and metabolic active lean tissue (42%). Plasma 3-methyl-histidine increased until Day 5 of fasting and then decreased, suggesting that protein sparing might follow early proteolysis. Daily steps count increased by 60% (P < 0.001) during the fasting period. Strength was maintained in non-weight-bearing muscles and increased in weight-bearing muscles (+33%, P < 0.001). Glycaemia, insulinemia, blood lipids, and blood pressure dropped during the fast (P < 0.05 for all), while non-esterified fatty acids and urinary beta-hydroxybutyrate increased (P < 0.01 for both). After a transient reduction, inflammatory cytokines returned to baseline at Day 10 of fasting, and LST were still lower than baseline values (-2.3% and -3.2%, respectively; P < 0.05 for both)., Conclusions: A 10 day fast appears safe in healthy humans. Protein loss occurs in early fast but decreases as ketogenesis increases. Fasting combined with physical activity does not negatively impact muscle function. Future studies will need to confirm these first findings., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)- Published
- 2021
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35. A dry immersion model of microgravity modulates platelet phenotype, miRNA signature, and circulating plasma protein biomarker profile.
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Twomey L, Navasiolava N, Robin A, Bareille MP, Gauquelin-Koch G, Beck A, Larcher F, Meade-Murphy G, Sheridan S, Maguire PB, Harrison M, Degryse B, Moyna NM, Gharib C, Custaud MA, and Murphy RP
- Subjects
- Adult, Biomarkers blood, Hemostasis, Humans, Male, Thrombosis metabolism, Blood Platelets cytology, Blood Proteins metabolism, MicroRNAs genetics, Models, Biological, Weightlessness
- Abstract
Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment., (© 2021. The Author(s).)
- Published
- 2021
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36. Hibernating brown bears are protected against atherogenic dyslipidemia.
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Giroud S, Chery I, Arrivé M, Prost M, Zumsteg J, Heintz D, Evans AL, Gauquelin-Koch G, Arnemo JM, Swenson JE, Lefai E, Bertile F, Simon C, and Blanc S
- Subjects
- Animals, Atherosclerosis prevention & control, Dyslipidemias prevention & control, Hibernation, Ursidae physiology
- Abstract
To investigate mechanisms by which hibernators avoid atherogenic hyperlipidemia during hibernation, we assessed lipoprotein and cholesterol metabolisms of free-ranging Scandinavian brown bears (Ursus arctos). In winter- and summer-captured bears, we measured lipoprotein sizes and sub-classes, triglyceride-related plasma-enzyme activities, and muscle lipid composition along with plasma-levels of antioxidant capacities and inflammatory markers. Although hibernating bears increased nearly all lipid levels, a 36%-higher cholesteryl-ester transfer-protein activity allowed to stabilize lipid composition of high-density lipoproteins (HDL). Levels of inflammatory metabolites, i.e., 7-ketocholesterol and 11ß-prostaglandin F2α, declined in winter and correlated inversely with cardioprotective HDL2b-proportions and HDL-sizes that increased during hibernation. Lower muscle-cholesterol concentrations and lecithin-cholesterol acyltransferase activity in winter suggest that hibernating bears tightly controlled peripheral-cholesterol synthesis and/or release. Finally, greater plasma-antioxidant capacities prevented excessive lipid-specific oxidative damages in plasma and muscles of hibernating bears. Hence, the brown bear manages large lipid fluxes during hibernation, without developing adverse atherogenic effects that occur in humans and non-hibernators., (© 2021. The Author(s).)
- Published
- 2021
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37. Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear.
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Cussonneau L, Boyer C, Brun C, Deval C, Loizon E, Meugnier E, Gueret E, Dubois E, Taillandier D, Polge C, Béchet D, Gauquelin-Koch G, Evans AL, Arnemo JM, Swenson JE, Blanc S, Simon C, Lefai E, Bertile F, and Combaret L
- Subjects
- Animals, Bone Morphogenetic Proteins genetics, Disease Models, Animal, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Hindlimb Suspension, Male, Mice, Mice, Inbred C57BL, Muscular Atrophy genetics, Muscular Atrophy pathology, Quadriceps Muscle pathology, RNA-Seq, Signal Transduction, Time Factors, Transcriptome, Transforming Growth Factor beta genetics, Ursidae genetics, Bone Morphogenetic Proteins metabolism, Hibernation, Muscular Atrophy metabolism, Quadriceps Muscle metabolism, Transforming Growth Factor beta metabolism, Ursidae metabolism
- Abstract
Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-β/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-β inhibiting therapies already targeted to prevent muscle atrophy.
- Published
- 2021
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38. Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction.
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Givre L, Crola Da Silva C, Swenson JE, Arnemo JM, Gauquelin-Koch G, Bertile F, Lefai E, and Gomez L
- Abstract
Ischemic heart disease remains one of the leading causes of death worldwide. Despite intensive research on the treatment of acute myocardial infarction, no effective therapy has shown clinical success. Therefore, novel therapeutic strategies are required to protect the heart from reperfusion injury. Interestingly, despite physical inactivity during hibernation, brown bears ( Ursus arctos ) cope with cardiovascular physiological conditions that would be detrimental to humans. We hypothesized that bear serum might contain circulating factors that could provide protection against cell injury. In this study, we sought to determine whether addition of bear serum might improve cardiomyocyte survival following hypoxia-reoxygenation. Isolated mouse cardiomyocytes underwent 45 min of hypoxia followed by reoxygenation. At the onset of reoxygenation, cells received fetal bovine serum (FBS; positive control), summer (SBS) or winter bear serum (WBS), or adult serums of other species, as indicated. After 2 h of reoxygenation, propidium iodide staining was used to evaluate cell viability by flow cytometry. Whereas, 0.5% SBS tended to decrease reperfusion injury, 0.5% WBS significantly reduced cell death, averaging 74.04 ± 7.06% vs. 79.20 ± 6.53% in the FBS group. This cardioprotective effect was lost at 0.1%, became toxic above 5%, and was specific to the bear. Our results showed that bear serum exerts a therapeutic effect with an efficacy threshold, an optimal dose, and a toxic effect on cardiomyocyte viability after hypoxia-reoxygenation. Therefore, the bear serum may be a potential source for identifying new therapeutic molecules to fight against myocardial reperfusion injury and cell death in general., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Givre, Crola Da Silva, Swenson, Arnemo, Gauquelin-Koch, Bertile, Lefai and Gomez.)
- Published
- 2021
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39. Gravitational Experimental Platform for Animal Models, a New Platform at ESA's Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models.
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Bonnefoy J, Ghislin S, Beyrend J, Coste F, Calcagno G, Lartaud I, Gauquelin-Koch G, Poussier S, and Frippiat JP
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- Animals, Humans, Larva pathogenicity, Larva radiation effects, Mice, Models, Animal, Xenopus laevis physiology, Hypergravity adverse effects, Rodentia physiology, Space Flight, Weightlessness adverse effects
- Abstract
Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g., conducting hypergravity experiments to demonstrate the feasibility of a study before its implementation and to complement inflight experiments by comparing the effects of micro- and hypergravity. In this paper, we present a new platform called the Gravitational Experimental Platform for Animal Models (GEPAM), which has been part of European Space Agency (ESA)'s portfolio of ground-based facilities since 2020, to study the effects of altered gravity on aquatic animal models (amphibian embryos/tadpoles) and mice. This platform comprises rotors for hypergravity exposure (three aquatic rotors and one rodent rotor) and models to simulate microgravity (cages for mouse hindlimb unloading and a random positioning machine (RPM)). Four species of amphibians can be used at present. All murine strains can be used and are maintained in a specific pathogen-free area. This platform is surrounded by numerous facilities for sample preparation and analysis using state-of-the-art techniques. Finally, we illustrate how GEPAM can contribute to the understanding of molecular and cellular mechanisms and the identification of countermeasures.
- Published
- 2021
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40. Specific shifts in the endocannabinoid system in hibernating brown bears.
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Boyer C, Cussonneau L, Brun C, Deval C, Pais de Barros JP, Chanon S, Bernoud-Hubac N, Daira P, Evans AL, Arnemo JM, Swenson JE, Gauquelin-Koch G, Simon C, Blanc S, Combaret L, Bertile F, and Lefai E
- Abstract
In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear's peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.
- Published
- 2020
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41. Simulated microgravity disturbs iron metabolism and distribution in humans: Lessons from dry immersion, an innovative ground-based human model.
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Nay K, Koechlin-Ramonatxo C, Rochdi S, Island ML, Orfila L, Treffel L, Bareille MP, Beck A, Gauquelin-Koch G, Ropert M, Loréal O, and Derbré F
- Subjects
- Adult, Bed Rest adverse effects, Bilirubin blood, Ferritins blood, Hepcidins blood, Humans, Immersion, Liver metabolism, Male, Myoglobin blood, Spleen metabolism, Transferrin analysis, Weightlessness Simulation methods, Iron metabolism, Weightlessness Simulation adverse effects
- Abstract
The objective of the present study was to determine the effects of dry immersion, an innovative ground-based human model of simulated microgravity and extreme physical inactivity, on iron homeostasis and distribution. Twenty young healthy men were recruited and submitted to 5 days of dry immersion (DI). Fasting blood samples and MRI were performed before and after DI exposure to assess iron status, as well as hematological responses. DI increased spleen iron concentrations (SIC), whereas hepatic iron store (HIC) was not affected. Spleen iron sequestration could be due to the concomitant increase in serum hepcidin levels (P < .001). Increased serum unconjugated bilirubin, as well as the rise of serum myoglobin levels support that DI may promote hemolysis and myolysis. These phenomena could contribute to the concomitant increase of serum iron and transferrin saturation levels (P < .001). As HIC remained unchanged, increased serum hepcidin levels could be due both to higher transferrin saturation level, and to low-grade pro-inflammatory as suggested by the significant rise of serum ferritin and haptoglobin levels after DI (P = .003 and P = .003, respectively). These observations highlight the need for better assessment of iron metabolism in bedridden patients, and an optimization of the diet currently proposed to astronauts., (© 2020 Federation of American Societies for Experimental Biology.)
- Published
- 2020
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42. Vascular and Microvascular Dysfunction Induced by Microgravity and Its Analogs in Humans: Mechanisms and Countermeasures.
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Navasiolava N, Yuan M, Murphy R, Robin A, Coupé M, Wang L, Alameddine A, Gauquelin-Koch G, Gharib C, Li Y, and Custaud MA
- Abstract
Weightlessness and physical inactivity have deleterious cardiovascular effects. The space environment and its ground-based models offer conditions to study the cardiovascular effects of physical inactivity in the absence of other vascular risk factors, particularly at the macro- and microcirculatory levels. However, the mechanisms involved in vascular dysfunction and remodeling are not sufficiently studied in the context of weightlessness and its analogs including models of physical inactivity. Here, we summarize vascular and microvascular changes induced by space flight and observed in models of microgravity and physical inactivity and review the effects of prophylactic strategies (i.e., countermeasures) on vascular and microvascular function. We discuss physical (e.g., exercise, vibration, lower body negative pressure, and artificial gravity) and nutritional/pharmacological (e.g., caloric restriction, resveratrol, and other vegetal extracts) countermeasures. Currently, exercise countermeasure appears to be the most effective to protect vascular function. Although pharmacological countermeasures are not currently considered to fight vascular changes due to microgravity, nutritional countermeasures are very promising. Dietary supplements/natural health products, especially plant extracts, should be extensively studied. The best prophylactic strategy is likely a combination of countermeasures that are effective not only at the cardiovascular level but also for the organism as a whole, but this strategy remains to be determined., (Copyright © 2020 Navasiolava, Yuan, Murphy, Robin, Coupé, Wang, Alameddine, Gauquelin-Koch, Gharib, Li and Custaud.)
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- 2020
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43. Effectiveness of Resistive Vibration Exercise and Whey Protein Supplementation Plus Alkaline Salt on the Skeletal Muscle Proteome Following 21 Days of Bed Rest in Healthy Males.
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Kenny HC, Tascher G, Ziemianin A, Rudwill F, Zahariev A, Chery I, Gauquelin-Koch G, Barielle MP, Heer M, Blanc S, O'Gorman DJ, and Bertile F
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- Cross-Over Studies, Dietary Supplements, Humans, Male, Muscle, Skeletal, Proteome, Whey, Whey Proteins, Bed Rest adverse effects, Vibration
- Abstract
Muscle atrophy is a deleterious consequence of physical inactivity and is associated with increased morbidity and mortality. The aim of this study was to decipher the mechanisms involved in disuse muscle atrophy in eight healthy men using a 21 day bed rest with a cross-over design (control, with resistive vibration exercise (RVE), or RVE combined with whey protein supplementation and an alkaline salt (NEX)). The main physiological findings show a significant reduction in whole-body fat-free mass (CON -4.1%, RVE -4.3%, NEX -2.7%, p < 0.05), maximal oxygen consumption (CON -20.5%, RVE -6.46%, NEX -7.9%, p < 0.05), and maximal voluntary contraction (CON -15%, RVE -12%, and NEX -9.5%, p < 0.05) and a reduction in mitochondrial enzyme activity (CON -30.7%, RVE -31.3%, NEX -17%, p < 0.05). The benefits of nutrition and exercise countermeasure were evident with an increase in leg lean mass (CON -1.7%, RVE +8.9%, NEX +15%, p < 0.05). Changes to the vastus lateralis muscle proteome were characterized using mass spectrometry-based label-free quantitative proteomics, the findings of which suggest alterations to cell metabolism, mitochondrial metabolism, protein synthesis, and degradation pathways during bed rest. The observed changes were partially mitigated during RVE, but there were no significant pathway changes during the NEX trial. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD006882. In conclusion, resistive vibration exercise, when combined with whey/alkalizing salt supplementation, could be an effective strategy to prevent skeletal muscle protein changes, muscle atrophy, and insulin sensitivity during medium duration bed rest.
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- 2020
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44. DI-5-Cuffs: Lumbar Intervertebral Disc Proteoglycan and Water Content Changes in Humans after Five Days of Dry Immersion to Simulate Microgravity.
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Treffel L, Navasiolava N, Mkhitaryan K, Jouan E, Zuj K, Gauquelin-Koch G, Custaud MA, and Gharib C
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- Adult, Back Pain etiology, Body Water metabolism, Humans, Intervertebral Disc diagnostic imaging, Lumbosacral Region diagnostic imaging, Male, Thigh blood supply, Vasoconstriction, Back Pain prevention & control, Compression Bandages, Intervertebral Disc metabolism, Proteoglycans metabolism, Weightlessness adverse effects
- Abstract
Most astronauts experience back pain after spaceflight, primarily located in the lumbar region. Intervertebral disc herniations have been observed after real and simulated microgravity. Spinal deconditioning after exposure to microgravity has been described, but the underlying mechanisms are not well understood. The dry immersion (DI) model of microgravity was used with eighteen male volunteers. Half of the participants wore thigh cuffs as a potential countermeasure. The spinal changes and intervertebral disc (IVD) content changes were investigated using magnetic resonance imaging (MRI) analyses with T1-T2 mapping sequences. IVD water content was estimated by the apparent diffusion coefficient (ADC), with proteoglycan content measured using MRI T1-mapping sequences centered in the nucleus pulposus. The use of thigh cuffs had no effect on any of the spinal variables measured. There was significant spinal lengthening for all of the subjects. The ADC and IVD proteoglycan content both increased significantly with DI (7.34 ± 2.23% and 10.09 ± 1.39%, respectively; mean ± standard deviation), p < 0.05). The ADC changes suggest dynamic and rapid water diffusion inside IVDs, linked to gravitational unloading. Further investigation is needed to determine whether similar changes occur in the cervical IVDs. A better understanding of the mechanisms involved in spinal deconditioning with spaceflight would assist in the development of alternative countermeasures to prevent IVD herniation., Competing Interests: The authors declare no conflict of interest.
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- 2020
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45. Cardiovascular System Under Simulated Weightlessness: Head-Down Bed Rest vs. Dry Immersion.
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Amirova L, Navasiolava N, Rukavishvikov I, Gauquelin-Koch G, Gharib C, Kozlovskaya I, Custaud MA, and Tomilovskaya E
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Background: The most applicable human models of weightlessness are -6° head-down bed rest (HDBR) and head-out dry immersion (DI). A detailed experimental comparison of cardiovascular responses in both models has not yet been carried out, in spite of numerous studies having been performed in each of the models separately., Objectives: We compared changes in central hemodynamics, autonomic regulation, plasma volume, and water balance induced by -6° HDBR and DI., Methods: Eleven subjects participated in a 21-day HDBR and 12 subjects in a 3-day DI. During exposure, measurements of the water balance, blood pressure, and heart rate were performed daily. Plasma volume evolution was assessed by the Dill-Costill method. In order to assess orthostatic tolerance time (OTT), central hemodynamic responses to orthostatic stimuli, and autonomous regulation, the 80° lower body negative pressure-tilt test was conducted before and right after both exposures., Results: For most of the studied parameters, the changes were co-directional, although they differed in their extent. The changes in systolic blood pressure and total peripheral resistance after HDBR were more pronounced than those after DI. The OTT was decreased in both groups: to 14.2 ± 3.1 min (vs. 27.9 ± 2.5 min before exposure) in the group of 21-day HDBR and to 8.7 ± 2.1 min (vs. 27.7 ± 1.2 min before exposure) in the group of 3-day DI., Conclusions: In general, cardiovascular changes during the 21-day HDBR and 3-day DI were co-directional. In some cases, changes in the parameters after 3-day DI exceeded changes after the 21-day HDBR, while in other cases the opposite was true. Significantly stronger effects of DI on cardiovascular function may be due to hypovolemia and support unloading (supportlessness)., (Copyright © 2020 Amirova, Navasiolava, Rukavishvikov, Gauquelin-Koch, Gharib, Kozlovskaya, Custaud and Tomilovskaya.)
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- 2020
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46. DI-5-CUFFS: Venoconstrictive Thigh Cuffs Limit Body Fluid Changes but Not Orthostatic Intolerance Induced by a 5-Day Dry Immersion.
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Robin A, Auvinet A, Degryse B, Murphy R, Bareille MP, Beck A, Gharib C, Gauquelin-Koch G, Daviet A, Larcher F, Custaud MA, and Navasiolava N
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Venoconstrictive thigh cuffs are used by cosmonauts to ameliorate symptoms associated with cephalad fluid shift. A ground simulation of microgravity, using the dry immersion (DI) model, was performed to assess the effects of thigh cuffs on body fluid changes and dynamics, as well as on cardiovascular deconditioning. Eighteen healthy men (25-43 years), randomly divided into two groups, (1) control group or (2) group with thigh cuffs worn 10 h/day, underwent 5-day DI. Cardiovascular responses to orthostatic challenge were evaluated using the lower body negative pressure (LBNP) test; body fluid changes were assessed by bio-impedance and hormonal assay; plasma volume evolution was estimated using hemoglobin-hematocrit; subjective tolerance was assessed by questionnaires. DI induced a decrease in plasma volume of 15-20%. Reduction in total body water of 3-6% stabilized toward the third day of DI. This reduction was derived mostly from the extracellular compartment. During the acute phase of DI, thigh cuffs limited the decrease in renin and the increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), the loss in total body water, and tended to limit the loss in calf volume, extracellular volume and plasma volume. At the later stable phase of DI, a moderate protective effect of thigh cuffs remained evident on the body fluids. Orthostatic tolerance time dropped after DI without significant difference between groups. Thigh cuff countermeasure slowed down and limited the loss of body water and tended to limit plasma loss induced by DI. These observed physiological responses persisted during periods when thigh cuffs were removed. However, thigh cuffs did not counteract decreased tolerance to orthostatic challenge., (Copyright © 2020 Robin, Auvinet, Degryse, Murphy, Bareille, Beck, Gharib, Gauquelin-Koch, Daviet, Larcher, Custaud and Navasiolava.)
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- 2020
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47. MicroRNAs facilitate skeletal muscle maintenance and metabolic suppression in hibernating brown bears.
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Luu BE, Lefai E, Giroud S, Swenson JE, Chazarin B, Gauquelin-Koch G, Arnemo JM, Evans AL, Bertile F, and Storey KB
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- Animals, Hibernation physiology, MicroRNAs metabolism, Muscle, Skeletal physiology, Muscular Atrophy genetics, Muscular Atrophy metabolism, RNA, Messenger genetics, Signal Transduction genetics, Ursidae metabolism, Ursidae physiology, Hibernation genetics, MicroRNAs genetics, Muscle, Skeletal metabolism, Ursidae genetics
- Abstract
Hibernating brown bears, Ursus arctos, undergo extended periods of inactivity and yet these large hibernators are resilient to muscle disuse atrophy. Physiological characteristics associated with atrophy resistance in bear muscle have been examined (e.g., muscle mechanics, neural activity) but roles for molecular signaling/regulatory mechanisms in the resistance to muscle wasting in bears still require investigation. Using quantitative reverse transcription PCR (RT-qPCR), the present study characterized the responses of 36 microRNAs linked with development, metabolism, and regeneration of skeletal muscle, in the vastus lateralis of brown bears comparing winter hibernating and summer active animals. Relative levels of mRNA of selected genes (mef2a, pax7, id2, prkaa1, and mstn) implicated upstream and downstream of the microRNAs were examined. Results indicated that hibernation elicited a myogenic microRNA, or "myomiR", response via MEF2A-mediated signaling. Upregulation of MEF2A-controlled miR-1 and miR-206 and respective downregulation of pax7 and id2 mRNA are suggestive of responses that promote skeletal muscle maintenance. Increased levels of metabolic microRNAs, such as miR-27, miR-29, and miR-33, may facilitate metabolic suppression during hibernation via mechanisms that decrease glucose uptake and fatty acid oxidation. This study identified myomiR-mediated mechanisms for the promotion of muscle regeneration, suppression of ubiquitin ligases, and resistance to muscle atrophy during hibernation mediated by observed increases in miR-206, miR-221, miR-31, miR-23a, and miR-29b. This was further supported by the downregulation of myomiRs associated with a muscle injury and inflammation (miR-199a and miR-223) during hibernation. The present study provides evidence of myomiR-mediated signaling pathways that are activated during hibernation to maintain skeletal muscle functionality in brown bears., (© 2019 Wiley Periodicals, Inc.)
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- 2020
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48. Limited Oxidative Stress Favors Resistance to Skeletal Muscle Atrophy in Hibernating Brown Bears ( Ursus Arctos ).
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Chazarin B, Ziemianin A, Evans AL, Meugnier E, Loizon E, Chery I, Arnemo JM, Swenson JE, Gauquelin-Koch G, Simon C, Blanc S, Lefai E, and Bertile F
- Abstract
Oxidative stress, which is believed to promote muscle atrophy, has been reported to occur in a few hibernators. However, hibernating bears exhibit efficient energy savings and muscle protein sparing, despite long-term physical inactivity and fasting. We hypothesized that the regulation of the oxidant/antioxidant balance and oxidative stress could favor skeletal muscle maintenance in hibernating brown bears. We showed that increased expressions of cold-inducible proteins CIRBP and RBM3 could favor muscle mass maintenance and alleviate oxidative stress during hibernation. Downregulation of the subunits of the mitochondrial electron transfer chain complexes I, II, and III, and antioxidant enzymes, possibly due to the reduced mitochondrial content, indicated a possible reduction of the production of reactive oxygen species in the hibernating muscle. Concomitantly, the upregulation of cytosolic antioxidant systems, under the control of the transcription factor NRF2, and the maintenance of the GSH/GSSG ratio suggested that bear skeletal muscle is not under a significant oxidative insult during hibernation. Accordingly, lower levels of oxidative damage were recorded in hibernating bear skeletal muscles. These results identify mechanisms by which limited oxidative stress may underlie the resistance to skeletal muscle atrophy in hibernating brown bears. They may constitute therapeutic targets for the treatment of human muscle atrophy., Competing Interests: The authors declare no conflict of interest.
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- 2019
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49. Multi-System Adaptation to Confinement During the 180-Day Controlled Ecological Life Support System (CELSS) Experiment.
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Yuan M, Custaud MA, Xu Z, Wang J, Yuan M, Tafforin C, Treffel L, Arbeille P, Nicolas M, Gharib C, Gauquelin-Koch G, Arnaud L, Lloret JC, Li Y, and Navasiolava N
- Abstract
Confinement experiments are essential to prepare long-term space exploration. The 180-day Chinese CELSS (Controlled Ecological Life Support System) study is unique in its design, including a closed-loop system and mid-mission simulation of Mars-like day-night cycle of 24 h 40 min for 36 days (days 72-108). Our aim was to study physiological and psychological consequences of this confinement in four healthy volunteers (one female). CELSS platform consisted of six interconnected modules including four greenhouses. Life support systems were controlled automatically. Body composition, fluid compartments, metabolic state, heart, large vessels, endothelial function, and muscle tone were studied using biological, functional, and/or morphological measurements. Behavioral activities were studied by ethological monitoring; psychological state was assessed by questionnaires. Body weight decreased by ∼2 kg mostly due to lean mass loss. Plasma volume and volume-regulating hormones were mostly stable. Carotid intima-media thickness (IMT) increased by 10-15%. Endothelium-dependent vasodilation decreased. Masseter tone increased by 6-14% suggesting stress, whereas paravertebral muscle tone diminished by 10 ± 6%. Behavioral flow reflecting global activity decreased 1.5- to 2-fold after the first month. Psychological questionnaires revealed decrease in hostility and negative emotions but increase in emotional adaptation suggesting boredom and monotony. One subject was clearly different with lower fitness, higher levels of stress and anxiety, and somatic signs as back pain, peak in masseter tone, increased blood cortisol and C-reactive protein. Comparison of CELSS experiment with Mars500 confinement program suggests the need for countermeasures to prevent increased IMT and endothelial deconditioning. Daily activity in greenhouse could act as countermeasure against psycho-physiological deconditioning.
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- 2019
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50. Metabolic reprogramming involving glycolysis in the hibernating brown bear skeletal muscle.
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Chazarin B, Storey KB, Ziemianin A, Chanon S, Plumel M, Chery I, Durand C, Evans AL, Arnemo JM, Zedrosser A, Swenson JE, Gauquelin-Koch G, Simon C, Blanc S, Lefai E, and Bertile F
- Abstract
Background: In mammals, the hibernating state is characterized by biochemical adjustments, which include metabolic rate depression and a shift in the primary fuel oxidized from carbohydrates to lipids. A number of studies of hibernating species report an upregulation of the levels and/or activity of lipid oxidizing enzymes in muscles during torpor, with a concomitant downregulation for glycolytic enzymes. However, other studies provide contrasting data about the regulation of fuel utilization in skeletal muscles during hibernation. Bears hibernate with only moderate hypothermia but with a drop in metabolic rate down to ~ 25% of basal metabolism. To gain insights into how fuel metabolism is regulated in hibernating bear skeletal muscles, we examined the vastus lateralis proteome and other changes elicited in brown bears during hibernation., Results: We show that bear muscle metabolic reorganization is in line with a suppression of ATP turnover. Regulation of muscle enzyme expression and activity, as well as of circulating metabolite profiles, highlighted a preference for lipid substrates during hibernation, although the data suggested that muscular lipid oxidation levels decreased due to metabolic rate depression. Our data also supported maintenance of muscle glycolysis that could be fuelled from liver gluconeogenesis and mobilization of muscle glycogen stores. During hibernation, our data also suggest that carbohydrate metabolism in bear muscle, as well as protein sparing, could be controlled, in part, by actions of n-3 polyunsaturated fatty acids like docosahexaenoic acid., Conclusions: Our work shows that molecular mechanisms in hibernating bear skeletal muscle, which appear consistent with a hypometabolic state, likely contribute to energy and protein savings. Maintenance of glycolysis could help to sustain muscle functionality for situations such as an unexpected exit from hibernation that would require a rapid increase in ATP production for muscle contraction. The molecular data we report here for skeletal muscles of bears hibernating at near normal body temperature represent a signature of muscle preservation despite atrophying conditions., Competing Interests: The study was approved by the Swedish Ethical Committee on Animal Experiment (applications #C212/9, #C47/9, #C7/12, #C268/12, and #C18/15), the Swedish Environmental Protection Agency (NV-0758-14), and the Swedish Board of Agriculture (31-11,102/12). All procedures complied with Swedish laws and regulations. Additionally, the samples obtained from captive bears had been collected after the animals had been euthanized, and were kindly provided by the Norwegian Veterinary Institute, and the Orsa Predator Park in Sweden (permit N° Dnr5.8.18-06068/2017).The authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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- 2019
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