Role of pattern recognition receptors and microbiota-derived ligands in obesity

Obesity is associated with activation of low-grade inflammation in tissues metabolically relevant for the regulation glucose homeostasis. The gut microbiota has been extensively linked to the inflammatory responses observed during obesity emphasizing the interconnection between host immunity and metabolism during obesity. Gut microbiota together with alteration of the gut barrier functions provide a myriad of circulating ligands for the pattern recognition receptors (PRRs) expressed in innate immune cells and nonimmune cells. PRR-dependent signalling drives the expression of a wide range of genes beyond the inflammatory response depending on the specific functions of the targeted cells and on the physiological context. PRRs activation can have opposite effects on host metabolic inflammation. Nucleotide-binding oligomerization domain 1 (NOD1) or NOD-like Receptor pyrin domain containing 3 (NLRP3) activation promote metabolic inflammation and insulin resistance while NOD2 activation improves insulin sensitivity and glucose homeostasis during obesity. Toll-like receptors (TLRs) 2, 4 and 5 also display specific effects on metabolic tissues. TLR5 deficient mice are prone to obesity and inflammation in response to high fat diet, while injection of TLR5 ligand, flagellin, has a protective effect toward diet-induced obesity. To the opposite TLR2 and 4 activations are associated with deleterious metabolic outcome during obesity. TLR4 activation enhances metabolic inflammation and insulin resistance and TLR2 via its activation by molecules derived from the gut microbiota favours the onset of obesity. It is now clear that activation of PRRs by bacterial derived molecules plays a key role in the host metabolic regulation. PRRs are expressed in various cell types complicating the understanding of the mechanisms underlying the relationship between PRRs activation/silencing and metabolic inflammation in obesity context. This review presents an overview of the current understanding of the interrelationship between the gut microbiota and PRRs, with a focus on its consequences for obesity and related metabolic diseases

Phenotypic effects of genetic variants associated with autism

While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants

Effect of particle microstructure and the role of proton on the lithium insertion properties of HTiNbO5 electrode material

International audienceLayered oxides showing edge-sharing octahedra are promising negative electrode materials for high-power Li-ion batteries. In this sense, we propose the synthesis of the lamellar HTiNbO5 by solid-state (SS), sol-gel (SG) and exfoliation-restacking (NS) syntheses investigating in the same way the charge storage mechanism of this oxide and the influence of the microstructure on material and electrochemical properties. An arsenal of character-ization techniques has been used to investigate these three types of particles using X-Ray Diffraction (XRD), electron microscopy, but also by associating mass spectroscopy to thermogravimetric analyses (TGA). Their ability to intercalate lithium has been compared, showing interesting and very similar specific capacities for solid-state and sol-gel synthesis (> 100 mAh.g -1 at 0.5 A.g -1). In addition, it was shown that the synthesis giving rise to nanosheet (NS) led to lower performance due to the presence of organic molecules in the interlayer spacing of the 2D lamellar structure. Lastly, in situ XRD evidenced a solid-solution reaction for HTiNbO5, with an initial and irreversible phase change leading to the formation of Li0.4HTiNbO5. Moreover, ex situ 1H MAS NMR measurements highlight the essential role of the proton in the charge storage mechanism of HTiNbO5. Thus, this paper demonstrates the interest of HTiNbO5 as a fast negative electrode material for high-power Li-ion batteries as well as the predominant role that the proton can play in the diffusion of lithium ions inside a confined interlayer space

Glucose but Not Fructose Alters the Intestinal Paracellular Permeability in Association With Gut Inflammation and Dysbiosis in Mice

International audienceA causal correlation between the metabolic disorders associated with sugar intake and disruption of the gastrointestinal (GI) homeostasis has been suggested, but the underlying mechanisms remain unclear. To unravel these mechanisms, we investigated the effect of physiological amounts of fructose and glucose on barrier functions and inflammatory status in various regions of the GI tract and on the cecal microbiota composition. C57BL/6 mice were fed chow diet and given 15% glucose or 15% fructose in drinking water for 9 weeks. We monitored caloric intake, body weight, glucose intolerance, and adiposity. The intestinal paracellular permeability, cytokine, and tight junction protein expression were assessed in the jejunum, cecum, and colon. In the cecum, the microbiota composition was determined. Glucose-fed mice developed a marked increase in total adiposity, glucose intolerance, and paracellular permeability in the jejunum and cecum while fructose absorption did not affect any of these parameters. Fructose-fed mice displayed increased circulation levels of IL6. In the cecum, both glucose and fructose intake were associated with an increase in Il13, Ifng, and Tnfa mRNA and MLCK protein levels. To clarify the relationships between monosaccharides and barrier function, we measured the permeability of Caco-2 cell monolayers in response to IFNg+TNFa in the presence of glucose or fructose. In vitro, IFNg+TNFa-induced intestinal permeability increase was less pronounced in response to fructose than glucose. Mice treated with glucose showed an enrichment of Lachnospiracae and Desulfovibrionaceae while the fructose increased relative abundance of Lactobacillaceae. Correlations between proinflammatory cytokine gene expression and bacterial abundance highlighted the potential role of members of Desulfovibrio and Lachnospiraceae NK4A136 group genera in the inflammation observed in response to glucose intake. The increase in intestinal inflammation and circulating levels of IL6 in response to fructose was observed in the absence of intestinal permeability modification, suggesting that the intestinal permeability alteration does not precede the onset of metabolic outcome (low-grade inflammation

Polycationic oxides as potential electrode materials for aqueous-based electrochemical capacitors

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Two phases model of ageing in mice: towards a better identification of age-related and late-life metabolic decline [Registered Report Stage 1 Protocol]

Abstract: Since being described in Drosophila melanogaster in 2011, the Smurf phenotype, has been seen to be evolutionarily conserved in nematode and zebrafish, and has helped to identify the discontinuous nature of ageing and predict impending death from natural causes as well as from environmental stresses. This phenotype allowed us to model ageing as being made of two successive phases : a phase A where individuals are healthy and have no risk of mortality but an age-dependent increasing risk of entering phase B, followed by a phase B where individuals show the so-called hallmarks of ageing and a high risk of death. We will test here whether these two consecutive phases of ageing separated by the Smurf transition are a conserved feature of ageing in the classical mammalian laboratory model Mus musculus. Thanks to a longitudinal longevity study using both males and females from two different mouse genetic backgrounds and by integrating physiological, metabolic and molecular measurements with the life history of approximately 150 mice, we are attempting to identify a phenotypic signature typical of the last phase of life, observable at any chronological age. Validating the two-phase ageing model in a mammalian organism would allow the high risk of imminent death to be better characterized in this model and would extend its implications to a broader range of species for aging research. </p

Vanadium and tungsten nitride thin film electrodes for micro-supercapacitor

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Cardiac rehabilitation and 5-year mortality after acute coronary syndromes: The 2005 French FAST-MI study.

IF 2.271International audienceBackground. - Clinical studies have shown a beneficial effect of cardiac rehabilitation (CR) on mortality.Objective. - To study the effect of CR prescription at discharge on 5-year mortality in patients with acute myocardial infarction (AMI).Methods. - Participants, from the 2005 French FAST-MI hospital registry, were 2894 survivors at discharge, divided according to AMI type: ST-segment elevation myocardial infarction (STEMI; n=1523) and non-STEMI (NSTEMI; n=1371). The effect of CR prescription on mortality was analysed using a Cox proportional hazards model.Results. - At discharge, 22.1% of patients had a CR prescription. Patients referred to CR were younger (62.4 vs. 67.5 years), were more frequently men and more had presented with STEMI (67.8% vs. 48.3%) than non-referred patients. Ninety-four (14.7%) deaths occurred among patients referred to CR and 585 (25.9%) among non-referred patients (P= 60 years) and AMI type showed that the inverse association was stronger in men (HR 0.64, 95% CI 0.48-0.87) than in women (HR 0.95, 95% CI 0.64-1.39), in younger (HR 0.34, 95% CI 0.15-0.77) than in older patients (HR 0.84, 95% CI 0.65-1.07) and in NSTEMI (HR 0.63, 95% CI 0.46-0.88) than in STEMI (HR 0.99, 95% CI 0.69-1.40).Conclusion. - After hospitalization for AMI, referral to CR remains a significant predictor of improved patient survival; some subgroups seem to gain greater benefit. (C) 2015 Elsevier Masson SAS. All rights reserved