Accumulation and Changes in Composition of Collagens in Subcutaneous Adipose Tissue After Bariatric Surgery

International audienceExtracellular matrix (ECM) in sc adipose tissue (scAT) undergoes pathological remodeling during obesity. However, its evolution during weight loss remains poorly explored.Objective:The objective of the investigation was to study the histological, transcriptomic, and physical characteristics of scAT ECM remodeling during the first year of bariatric surgery (BS)-induced weight loss and their relationships with metabolic and bioclinical improvements.Design, Setting, Patients, and Interventions:A total of 118 morbidly obese candidates for BS were recruited and followed up during 1 year after BS.Main Outcome Measures:scAT surgical biopsy and needle aspiration as well as scAT stiffness measurement were performed in three subgroups before and after BS. Fourteen nonobese, nondiabetic subjects served as controls.Results:Significantly increased picrosirius-red-stained collagen accumulation in scAT after BS was observed along with fat mass loss, despite metabolic and inflammatory improvements and undetectable changes of scAT stiffness. Collagen accumulation positively associated with M2-macrophages (CD163+ cells) before BS but negatively afterward. Expression levels of genes encoding ECM components (eg, COL3A1, COL6A1, COL6A2, ELN), cross-linking enzymes (eg, lysyl oxidase [LOX], LOXL4, transglutaminase), metalloproteinases, and their inhibitors were modified 1 year after BS. LOX expression and protein were significantly decreased and associated with decreased fat mass as well as other cross-linking enzymes. Although total collagen I and VI staining decreased 1 year after BS, we found increased degraded collagen I and III in scAT, suggesting increased degradation.Conclusions:After BS-induced weight loss and related metabolic improvements, scAT displays major collagen remodeling with an increased picrosirius-red staining that relates to increased collagen degradation and importantly decreased cross-linking. These features are in agreement with adequate ECM adaptation during fat mass loss- See more at: http://press.endocrine.org/doi/10.1210/jc.2015-3348#sthash.PLeUvzKd.dpu

Aorto-duodenal fistula secondary to aortic graft replacement.

peer reviewedSecondary aorto-duodenal fistula (SADF) is a rare and serious event occurring in up to 45% of aortic prosthesis infections. The clinical manifestations are variable ranging from isolated signs of graft infection such as fever to massive gastrointestinal bleeding. The diagnosis is based on CT scan and is generally oriented by an inconstant association of indirect signs. Despite a high early severe postoperative morbidity and mortality, especially in presence of a preoperative shock, emergency surgery allows for the diagnosis and treatment of SADF with multidisciplinary management allowing favorable midterm outcomes among surviving patients. The images that we present in this manuscript highlight some indirect signs of SADF on CT scan that should alert clinicians to warrant on time surgical management with an illustration of per operative diagnosis of the fistula

Comparative analysis of the duodenojejunal microbiome with the oral and fecal microbiomes reveals its stronger association with obesity and nutrition

The intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While most research focuses on the fecal microbiota due to its easier accessibility, the small intestine, as a major site for nutrient sensing and absorption, warrants further investigation to determine its microbiota composition and functions. Here, we conducted a clinical research project in 30 age- and sex-matched participants with (n = 15) and without (n = 15) obesity. Duodenojejunal fluid was obtained by aspiration during endoscopy. Phenotyping included clinical variables related to metabolic status, lifestyle, and psychosocial factors using validated questionnaires. We performed metagenomic analyses of the oral, duodenojejunal, and fecal microbiome, alongside metabolomic data from duodenojejunal fluid and feces, integrating these data with clinical and lifestyle information. Our results highlight significant associations between duodenojejunal microbiota composition and usual dietary intake, as well as clinical phenotypes, with larger effect sizes than the associations between these variables and fecal microbiota. Notably, we found that the duodenojejunal microbiota of patients with obesity exhibited higher diversity and showed distinct differences in the abundance of several duodenojejunal microbiota species compared with individuals without obesity. Our findings support the relevance of studying the role of the small intestinal microbiota in the pathogenesis of nutrition-related diseases

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Precision Bariatric/Metabolic Medicine and Surgery

Indications and techniques of bariatric surgery (BS) have constantly evolved in recent decades and now face new challenges [...

Assessement of intestinal permeability in human obesity

Chez les rongeurs rendus obèses par un régime hyper-lipidique, un changement du microbiote est associé à une altération de la perméabilité intestinale, augmentant le passage d’antigènes alimentaires ou bactériens et contribuant à une inflammation chronique de bas grade et une insulinorésistance. Cependant chez l’homme, les modifications de perméabilité intestinale, son impact sur les altérations métaboliques, inflammatoires systémiques et tissulaires sont peu documentées. L’objectif de ce travail est de caractériser la perméabilité intestinale (i.e. jéjunum) et les mécanismes impliqués dans sa régulation dans l’obésité humaine sévère en conditions de jeûne (basal) et après un apport aigu de lipides selon des approches complémentaires in vivo (biomarqueurs), ex vivo (chambre de Ussing, étude des protéines de jonctions serrées en immunofluorescence) et in vitro (lignée cellulaire Caco-2/TC7). A l’état basal nous avons observé une diminution de la localisation de l’occludine et de la tricelluline dans les jonctions serrées au niveau du jéjunum et des taux circulants en zonuline et LPS binding protéine plus élevés chez les obèses. La perméabilité Jéjunale basale mesurée ex vivo en chambre de Ussing était comparable entre obèses et non obèses avec cependant des liens entre ces mesures et les paramètres de l’inflammation systémique chez les patients obèses (CRP et Haptoglobine). Une charge unique en lipides alimentaires, entrainait une augmentation rapide et significative de la perméabilité aux macromolécules (FITC-Dextran 4 kDa) in vitro et ex vivo, démontrant ainsi l’effet direct des lipides postprandiaux sur la barrière épithéliale. La perméabilité aux macromolécules après exposition aux lipides était plus élevée chez les patients obèses à fortiori diabétiques de type 2 et était associée à l’inflammation systémique (CRP) et intestinale (calprotectine fécale). Ainsi, nos résultats mettent en évidence un défaut de la barrière intestinale dans l'obésité caractérisée par une hyperperméabilité jéjunale démasquée par les lipides alimentaires et associée à l’inflammation et aux troubles métaboliques.Intestinal barrier damage is associated with low-grade inflammation and metabolic impairment in rodent models of obesity. Whether intestinal permeability is altered in human metabolic disorders remains poorly investigated. Using a large cohort of well-characterized obese subjects and a human enterocyte model, we examined intestinal permeability in the basal state and after a challenge by a lipid load. We showed a reduction of occludin and tricellulin at jejunal tight junctions and increased serum levels of zonulin and LPS-Binding Protein in obese subjects. Jejunal permeability, directly measured in Ussing chambers in the fasting condition, was not significantly increased compared to non-obese subjects. Nevertheless, within the obese cohort, high permeability was associated with systemic inflammation (CRP and haptoglobin). A single lipid load increased permeability both in Caco-2/TC7 cells and ex vivo in human jejunum, demonstrating dietary lipids’ direct effects on the epithelial barrier. Permeability after the lipid load was significantly higher in the jejunum of obese subjects and associated with systemic and intestinal inflammation (CRP and fecal calprotectin) and type 2 diabetes. Thus, our results highlight an intestinal barrier defect in obesity, with a jejunal permeability increased by a lipid challenge and linked to inflammatory and metabolic impairments