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

La fibrose du tissu adipeux

Dans des conditions obésogènes, l’expansion du tissu adipeux (TA) correspond à une réponse physiologique nécessaire au stockage du surplus énergétique. Cependant, la chronicisation de l’obésité conduit à un remodelage pathologique du TA, incluant un épaississement de la matrice extracellulaire caractéristique d’un état fibrotique. Ces modifications du TA affectent localement ses fonctions endocrines et de stockage. Elles contribuent ensuite aux altérations des dialogues inter-organes. D’autres organes comme le foie et les muscles vont aussi voir leur biologie perturbée. La compréhension des mécanismes à l’origine du remodelage pathologique du TA et de ses conséquences sur les comorbidités de l’obésité permettrait de développer de nouvelles stratégies de traitement pour ces pathologies complexes

La fibrose du tissu adipeux

International audienceObesity can be defined as the adaptive response of organism facing chronic nutrient overflow. In this context, the adipose tissue (AT) can expand, through increased adipocyte size and number, to function as the main energy-storing organ. However, over the course of obesity progression, the AT undergo continual remodeling, evolving into pathological alterations. It is now clear that pro-inflammatory cell accumulation favors local AT injury. More recently, we and others described excess levels of extracellular matrix (ECM) and fibrosis in AT depots from obese individuals. In obese mice, targeting ECM-remodeling improves glucose tolerance and insulin sensitivity. Therefore AT fibrosis represents a maladaptive mechanism contributing to obesity-related metabolic complications such as diabetes, cardiometabolic and liver diseases. Here, we review the current knowledge about obesity-induced adipose tissue remodeling and its local and systemic consequences.Dans des conditions obésogènes, l’expansion du tissu adipeux (TA) correspond à une réponse physiologique nécessaire au stockage du surplus énergétique. Cependant, la chronicisation de l’obésité conduit à un remodelage pathologique du TA, incluant un épaississement de la matrice extracellulaire caractéristique d’un état fibrotique. Ces modifications du TA affectent localement ses fonctions endocrines et de stockage. Elles contribuent ensuite aux altérations des dialogues inter-organes. D’autres organes comme le foie et les muscles vont aussi voir leur biologie perturbée. La compréhension des mécanismes à l’origine du remodelage pathologique du TA et de ses conséquences sur les comorbidités de l’obésité permettrait de développer de nouvelles stratégies de traitement pour ces pathologies complexes

The multifaceted progenitor fates in healthy or unhealthy adipose tissue during obesity

International audienceWhile obesity is defined as an excessive fat accumulation conferring a risk to metabolic health, increased adipose mass by itself does not fully explain obesity’s propensity to promote metabolic alterations. Adipose tissue regulates multiple processes critical for energy homeostasis and its dysfunction favors the development and perpetuation of metabolic diseases. Obesity drives inflammatory leucocyte infiltration in adipose tissue and fibrotic transformation of the fat depots. Both features associate with metabolic alterations such as impaired glucose control and resistance to fat mass loss. In this context, adipose progenitors, an heterogenous resident population of mesenchymal stromal cells, display functions important to shape healthy or unhealthy adipose tissue expansion. We, here, outline the current understanding of adipose progenitor biology in the context of obesity-induced adipose tissue remodeling

Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis

International audienceObesity originates from an imbalance between caloric intake and energy expenditure that promotes adipose tissue expansion, which is necessary to buffer nutrient excess. Patients with higher visceral fat mass are at a higher risk of developing severe complications such as type 2 diabetes and cardiovascular and liver diseases. However, increased fat mass does not fully explain obesity's propensity to promote metabolic diseases. With chronic obesity, adipose tissue undergoes major remodeling, which can ultimately result in unresolved chronic inflammation leading to fibrosis accumulation. These features drive local tissue damage and initiate and/or maintain multiorgan dysfunction. Here, we review the current understanding of adipose tissue remodeling with a focus on obesity-induced adipose tissue fibrosis and its relevance to clinical manifestations

The Safety and Efficacy of Hepatic Transarterial Embolization Using Microspheres and Microcoils in Patients with Symptomatic Polycystic Liver Disease

Purpose: We investigated the long-term safety and efficacy of hepatic transarterial embolization (TAE) in patients with symptomatic polycystic liver disease (PLD). Materials and Methods: A total of 26 patients were included, mean age of 52.3 years (range: 33–78 years), undergoing 32 TAE procedures between January 2012 and December 2019 were included in this retrospective study. Distal embolization of the segmental hepatic artery was performed with 300–500 µm embolic microspheres associated with proximal embolization using microcoils. The primary endpoint was clinical efficacy, defined by an improvement in health-related quality of life using a modified Short Form-36 Health Survey and improvement in symptoms (digestive or respiratory symptoms and chronic abdominal pain), without invasive therapy during the follow-up period. Secondary endpoints were a decrease in total liver volume and treated liver volume and complications. Results: Hepatic embolization was performed successfully in 30 of 32 procedures with no major adverse events. Clinical efficacy was 73% (19/26). The mean reduction in hepatic volume was −12.6% at 3 months and −27.8% at the last follow-up 51 ± 15.2 months after TAE (range: 30–81 months; both ps < 0.01). The mean visual analog scale pain score was 5.4 ± 2.8 before TAE and decreased to 2.7 ± 1.9 after treatment. Three patients had minor adverse events, and one patient had an adverse event of moderate severity. Conclusion: Hepatic embolization using microspheres and microcoils is a safe and effective treatment for PLD that improves symptoms and reduces the volume of hepatic cysts

Percutaneous ultrasound-guided balloon-assisted embolization of iatrogenic femoral artery pseudoaneurysms with Glubran®2 cyanoacrylate glue: safety, efficacy and outcomes

International audienceBackground: Femoral pseudoaneurysm (PA) is a frequent complication of arterial access for endovascular procedures. Surgery has traditionally been considered as the gold standard of therapy. We aimed to report our experience of percutaneous ultrasound (US)-guided balloon-assisted embolization with cyanoacrylate glue for the treatment of iatrogenic femoral PAs.Methods: Retrospective two-center study of patients with femoral iatrogenic PAs treated by N-butyl cyanoacrylate-methacryloxy sulfolane (INCA-MS) Glubran (R) 2 glue embolization between July 2013 and November 2017. All patients underwent contralateral arterial access with balloon placement of an appropriate size in front of the PA neck before glue/lipiodol embolization in a 1:1 ratio by percutaneous US-guided puncture of the aneurysmal sac under fluoroscopy control.Results: Twenty-three patients (12 females, 11 males; median age, 79 years; range, 18-93 years) were included. Median PA size was 34 mm (range, 17-60 mm). The median time to treatment was 5 days (range, 1-30 days). Twenty patients (86.9%) were successfully treated by glue injection alone. The three remaining patients (13.1%) with persistent PA or associated arterial-venous fistula were immediately treated during the same procedure by additional stent-graft. Then, overall immediate and 1-month clinical success rates were 100%. No surgical conversion was necessary. No recurrence was reported during the median follow-up of 11 months (range, 2-73 months). Two (8.7%) puncture-related complications occurred at the contralateral arterial access site, which spontaneously resolved. No non-target glue embolization occurred.Conclusions: US-guided balloon-assisted glue embolization is safe and effective to treat iatrogenic femoral PAs in mast cases, offering complete exclusion of the PA and avoiding the morbidity of open surgery

Mechanical Thrombectomy in Acute Thrombosis of Dialysis Arteriovenous Fistulae and Grafts Using a Vacuum-Assisted Thrombectomy Catheter: A Multicenter Study.

PURPOSE To prospectively analyze technical and clinical outcome of percutaneous thrombectomy aspiration using a vacuum-assisted thrombectomy catheter in acutely thrombosed dialysis arteriovenous fistula (AVF) and/or arteriovenous graft (AVG). MATERIALS AND METHODS From June 2016 to April 2017, 35 patients (average age, 61.8 y; range, 33-81 y) presenting with acute thrombosis of dialysis AVF and/or AVG were prospectively evaluated for mechanical thrombectomy using the Indigo System. Adjunctive therapies and procedure-related complications were noted. Technical success, clinical success, primary patency, primary assisted patency, and secondary patency of the dialysis fistula were assessed. RESULTS Mean follow-up time was 8.5 months (range, 3-12 months). Technical success was 97.1% (34/35 patients). Clinical success was 91.4% (32/35 patients). Complications included hematoma (n = 1), thrombosis < 24 hours (n = 1), and perforation (n = 1). Other mechanical/aspiration thrombectomy devices were used in 1 site to clear the thrombus burden (Arrow-Trerotola [2.8%; 1/35 patients] and Fogarty [5.7%; 2/35 patients]). Average procedure time was 38.1 minutes (range, 15-140 min). Average blood loss during the procedure was 122.5 mL (range, 50-300 mL). The 6-month primary patency, primary assisted patency, and secondary patency were 71%, 80%, and 88.5%. No risk factors for early dialysis fistula occlusion were identified. There was no 30-day mortality. CONCLUSIONS Percutaneous mechanical thrombectomy aspiration of thrombosed dialysis AVF and/or AVG with a vacuum-assisted thrombectomy catheter is a safe procedure with a low complication rate and effective method for restoring patency before hemodialysis

Prostate Artery Embolization Using N-Butyl Cyanoacrylate Glue for Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Valid Alternative to Microparticles?

International audienceOur goal was to evaluate the feasibility, safety, and short-term outcomes of prostate artery embolization (PAE) with N-butyl cyanoacrylate (NBCA) glue as the only embolic agent in patients with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTSs). A two-center retrospective study of 50 patients (mean age, 67.6 ± 7.4 years; range, 54–85 years) treated with NBCA between 2017 and 2020 was conducted. PAE was performed using a mixture of Glubran 2 glue and Lipiodol in a 1:8 ratio, under local anesthesia, on an outpatient basis, after cone-beam computed tomography vascular mapping. Mean total injected NBCA/Lipiodol volume was 0.9 ± 0.3 mL, total injection time was 21.9 ± 7.8 s, and total radiation dose was 18,458 ± 16,397 mGy·cm. Statistically significant improvements over time occurred for the International Prostate Symptoms Score (9.9 ± 6.8 versus 20.5 ± 6.7, p = 0.0001), quality-of-life score (2.2 ± 1.5 versus 4.9 ± 1.0, p = 0.0001), prostate-specific antigen level (4.6 ± 3.0 versus 6.4 ± 3.7, p = 0.0001), and prostate volume (77.3 ± 30.5 versus 98.3 ± 40.2, p = 0.0001) at a median of 3 months versus baseline. Minor adverse events developed in 11/50 (22%) patients, but no major complications occurred. The International Index of Erectile Function did not change significantly. PAE with NBCA is feasible, safe, fast, and effective for patients with BPH-related LUTSs. Prospective comparative studies with longer follow-ups are warranted

Autophagy inhibition blunts PDGFRA adipose progenitors’ cell-autonomous fibrogenic response to high-fat diet

International audienceAdipose tissue (AT) fibrosis in obesity compromises adipocyte functions and responses to intervention-10 induced weight loss. It is driven by AT progenitors with dual fibro/adipogenic potential, but pro-fibrogenic pathways activated in obesity remain to be deciphered. To investigate the role of macroautophagy/autop-hagy in AT fibrogenesis, we used Pdgfra-Cre Ert2 transgenic mice to create conditional deletion of Atg7 alleles in AT progenitor cells (atg7 cKO) and examined sex-dependent, depot-specific AT remodeling in high-fat diet (HFD)-fed mice. Mice with atg7 cKO had markedly decreased extracellular matrix (ECM) gene expression in 15 visceral, subcutaneous, and epicardial adipose depots compared to Atg7 lox/lox littermates. ECM gene program regulation by autophagy inhibition occurred independently of changes in the mass of fat tissues or adipocyte numbers of specific depots, and cultured preadipocytes treated with pharmacological or siRNA-mediated autophagy disruptors could mimic these effects. We found that autophagy inhibition promotes global cell-autonomous remodeling of the paracrine TGF-BMP family landscape, whereas ECM gene modulation was 20 independent of the autophagic regulation of GTF2IRD1. The progenitor-specific mouse model of ATG7 inhibition confirms the requirement of autophagy for white/beige adipocyte turnover, and combined to in vitro experiments, reveal progenitor autophagy dependence for AT fibrogenic response to HFD, through the paracrine remodeling of TGF-BMP factors balance