Fifteen days of 3200m simulated hypoxia marginally regulates markers for protein synthesis and degradation in human skeletal muscle

Chronic hypoxia leads to muscle atrophy. The molecular mechanisms responsible for this phenomenon are not well defined in vivo. We sought to determine how chronic hypoxia regulates molecular markers of protein synthesis and degradation in human skeletal muscle and whether these regulations were related to the regulation of the hypoxia-inducible factor (HIF) pathway. Eight young male subjects lived in a normobaric hypoxic hotel (FiO2 14.1%, 3,200 m) for 15 days in well-controlled conditions for nutrition and physical activity. Skeletal muscle biopsies were obtained in the musculus vastus lateralis before (PRE) and immediately after (POST) hypoxic exposure. Intramuscular hypoxia-inducible factor-1 alpha (HIF-1α) protein expression decreased (-49%, P=0.03), whereas hypoxia-inducible factor-2 alpha (HIF-2α) remained unaffected from PRE to POST hypoxic exposure. Also, downstream HIF-1α target genes VEGF-A (-66%, P=0.006) and BNIP3 (-24%, P=0.002) were downregulated, and a tendency was measured for neural precursor cell expressed, developmentally Nedd4 (-47%, P=0.07), suggesting lowered HIF-1α transcriptional activity after 15 days of exposure to environmental hypoxia. No difference was found on microtubule-associated protein 1 light chain 3 type II/I (LC3b-II/I) ratio, and P62 protein expression tended to increase (+45%, P=0.07) compared to PRE exposure levels, suggesting that autophagy was not modulated after chronic hypoxia. The mammalian target of rapamycin complex 1 pathway was not altered as Akt, mammalian target of rapamycin, S6 kinase 1, and 4E-binding protein 1 phosphorylation did not change between PRE and POST. Finally, myofiber cross-sectional area was unchanged between PRE and POST. In summary, our data indicate that moderate chronic hypoxia differentially regulates HIF-1α and HIF-2α, marginally affects markers of protein degradation, and does not modify markers of protein synthesis or myofiber cross-sectional area in human skeletal muscle

The endocannabinoid system links gut microbiota to adipogenesis

We investigated several models of gut microbiota modulation: selective (prebiotics, probiotics, high-fat), drastic (antibiotics, germ-free mice) and mice bearing specific mutations of a key gene involved in the toll-like receptors (TLR) bacteria-host interaction (Myd88−/−). Here we report that gut microbiota modulates the intestinal endocannabinoid (eCB) system-tone, which in turn regulates gut permeability and plasma lipopolysaccharide (LPS) levels.The activation of the intestinal endocannabinoid system increases gut permeability which in turn enhances plasma LPS levels and inflammation in physiological and pathological conditions such as obesity and type 2 diabetes.The investigation of adipocyte differentiation and lipogenesis (both markers of adipogenesis) indicate that gut microbiota controls adipose tissue physiology through LPS-eCB system regulatory loops and may play a critical role in the adipose tissue plasticity during obesity.In vivo, ex vivo and in vitro studies indicate that LPS acts as a master switch on adipose tissue metabolism, by blocking the cannabinoid-driven adipogenesis

Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability

Background and aims: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Methods: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Results: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. Conclusion: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes

Oxidation behaviour of SiC/SiC ceramic matrix composites in air

Oxidation of silicon melt infiltrated SiC/SiC ceramic matrix composites (CMC) was studied in air at 1200–1400 °C for 1, 5, 24 and 48 h. Weight gain and oxide layer thickness measurements revealed the oxidation follows parabolic reaction kinetics with increase in temperature and time. XRD showed the extent of oxide layer (SiO2) formation was greatest after 48 h at 1400 °C: an observation confirmed by X-ray photoelectron spectroscopy (XPS), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM) analyses. Oxide layer thickness varied from 1 μm after 48 h at 1200 °C to 8 μm after 48 h at 1400 °C. Oxidation of SiC/SiC composites is both temperature and time dependent with an activation energy of 619 kJ mol−1. BN coatings around SiC fibres showed good resistance to oxidation even after 48 h at 1400 °C

Kinetic Processes in the CVD of SiC from CH3SiCl3-H2 in a Vertical Hot-Wall Reactor

The chemical vapour deposition of SiC-based ceramics from the CH3SiCl3-H2 precursor is investigated on the basis of large scale experimental and theoretical approaches. The use of a vetirtical cylindrical hot-wall LPCVD reactor permits to get a wide isothemal reaction zone with a creeping laminar flow around the substrate and a largely chemical control of the kinetics, which favours a high supersaturation and a nucleation regime. A calculation of the coverage of C (111) or Si(111) planes of SiC points out the importance of the chemisorption of SiCl3 and H radicals on C atoms and of CH3 and Cl radicals on Si atoms. On the basis of kinetic experiments and of chemical and structural investigations of the deposits, several domains of conditions are defined with different rnechanisms for the formation of SiC-based ceramics. For low temperatures and low pressures, a regime of growth of stoichiometric SiC microcrystals occurs from reaction of CH3 and SiCl3 intermediates. Higher pressures in the chemical control knetic domain, favour a regime of nucleation of nanocrystals with an excess of silicon resulting from SiCl3/SiCl2 silicon precursor

Si-C-N ceramics with a high microstructural stability elaborated from the pyrolysis of new polycarbosilazane precursors

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Chlorine and oxygen inhibition effects in the deposition of SiC-based ceramics from the Si-C-H-Cl system

International audienceThe inhibitory role of HCl and oxygen in the chemical vapour deposition of SiC-based ceramics from the SiCHCl system, is pointed out in terms of nucleation and growth process on the basis of experimental and theoretical approaches. The addition of HCl to methyltrichlorosilane MTS-H2 gaseous precursors (i) decreases the nucleation and growth rate, (ii) induces a transition from a diffusion to a reaction rate control of the deposition process, (iii) improves the smoothness of the films surface, (iv) results in a transition from anisotropic films with columnar microstructure and Si, C and O concentration gradients to nanocrystallized materials with quite constant Si, C and O contents. These behaviours are tentatively explained by assessments of the gas phase super saturation and calculations of the chemisorbed layer composition. The occurrence of oxygen within the nanocrystallized films is then related to the growth inhibition effect and the presence of silicon excess shown by EELS analyses

Correlations between gas phase supersaturation, nucleation process and physico-chemical characteristics of silicon carbide deposited from Si-C-H-Cl system on silica substrates

International audienceIn the CH3SiCl3-H2 CVD system, from which SiC-based films are prepared, the supersaturation of the gas phase increases when temperature and total pressure decreases and when a diffusion-controlled kinetic process is changed in a reaction-controlled one. These conditions variations seem to induce a transition from a growth regime to a nucleation regime, as evidenced by a study of the initial stages of the deposition. A transition from a crystallized film with columnar crystals to a nanocrystalline deposit is also reported on the basis of accurate experiments using TEM and related techniques