Dataset Information

Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis.

ABSTRACT: The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Functional studies were performed in HepG2 cells and primary hepatocytes. Surgery was associated with a decrease in the inflammatory response and revealed the role of mitogen-activated protein kinases. Nonalcoholic steatohepatitis was associated with an increased glutaminolysis-induced production of α-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy and affected methylation-related epigenomic remodelling enzymes. Hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. Our results suggest that the increased glutaminolysis-induced α-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation play a crucial role in the inefficient adaptive responses leading to steatohepatitis in obesity.

SUBMITTER: Cabre N

PROVIDER: S-EPMC9320342 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis.

Cabré Noemí N Luciano-Mateo Fedra F Chapski Douglas J DJ Baiges-Gaya Gerard G Fernández-Arroyo Salvador S Hernández-Aguilera Anna A Castañé Helena H Rodríguez-Tomàs Elisabet E París Marta M Sabench Fàtima F Castillo Daniel Del DD Del Bas Josep M JM Tomé Mercedes M Bodineau Clément C Sola-García Alejandro A López-Miranda José J Martín-Montalvo Alejandro A Durán Raúl V RV Vondriska Thomas M TM Rosa-Garrido Manuel M Camps Jordi J Menéndez Javier A JA Joven Jorge J

International journal of molecular sciences 20220715 14

The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Function ...[more]

PMID: 35887177

Similar Datasets

Project description:BackgroundLaparoscopic sleeve gastrectomy (LSG) modifies the upper gastrointestinal tract motility. Controversial data currently exist. The aim of the study was to evaluate esophageal motility before and after LSG.Patients and methodsMorbid obese patients scheduled for LSG underwent reflux symptoms evaluation and manometry preoperatively and postoperatively. The preoperative and postoperative results were compared and analyzed.ResultsEighteen patients were enrolled. Heartburn and regurgitation improved in 38.9% and 11.1% of the patients, but deteriorated in 11.1% and 27.8% of the patients, respectively. Lower esophageal sphincter (LES) total length decreased postoperatively (p=0.002). Resting and residual pressures tended to decrease postoperatively (mean difference [95% confidence interval]: -4 [-8.3/0.2] mmHg, p=0.060; -1.4 [-3/0.1] mmHg, p=0.071, respectively). Amplitude pressure decreased from 95.7±37.3 to 69.8±26.3 mmHg at the upper border of LES (p=0.014), and tended to decrease at the distal esophagus from 128.5±30.1 to 112.1±35.4 mmHg (p=0.06) and mid-esophagus from 72.7±34.5 to 49.4±16.7 mmHg (p=0.006). Peristaltic normal swallow percentage increased from 47.2±36.8 to 82.8±28% (p=0.003). Postoperative regurgitation was strongly negatively correlated with LES total length (Spearman's r=-0.670). When groups were compared according to heartburn status, statistical significance was observed between the groups of improvement and deterioration regarding postoperative residual pressure and postoperative relaxation (p<0.002, p<0.002, respectively). With regard to regurgitation status, there was statistically significant difference between groups regarding preoperative amplitude pressure at the upper border of LES (p<0.056).ConclusionPatients developed decreased LES length and weakened LES pressure after LSG. Esophageal body peristalsis was also affected in terms of decreased amplitude pressure, especially at the upper border of LES. Nevertheless, body peristalsis was normalized postoperatively. LSG might not deteriorate heartburn. Regurgitation might increase following LSG due to shortening of LES length, particularly in patients with range of preoperative amplitude pressure at the upper border of LES of 38.9-92.6 mmHg.

Project description:Metabolic surgery, including laparoscopic sleeve gastrectomy (LSG), may improve hypertension (HTN) complicated by severe obesity; however, insufficient deliberation exists regarding the therapeutic effect of post-metabolic surgery on HTN. This study aimed to analyze the factors correlated with HTN remission and recurrence post-LSG in patients who have severe obesity, and to create a classification system to predict HTN remission and recurrence. Of the 102 patients who underwent LSG at Iwate Medical University Hospital between 2008 and 2020, 62 were enrolled in this study. Factors correlated with HTN remission and recurrence post-LSG were retrospectively analyzed. The HTN remission rate 12-months post-LSG was 40.3%. The remission cohort had a lower number of preoperative antihypertensive drugs (ADs) than that of the non-remission cohort (one and two tablets, respectively; p< 0.001). Additionally, the remission cohort had a statistically significantly smaller visceral fat area (VFA) than that of the non-remission cohort, at all time points. Logistic regression analysis revealed that the number of preoperative ADs and VFA were independent predictors of remission. The HTN recurrence rate 36-months post-LSG was 36.0%. In the recurrence cohort, the number of preoperative ADs and VFA were higher and larger than that in the non-recurrence cohort, respectively. Stratification, based on the number of preoperative ADs and VFA, revealed that the HTN remission and recurrence rates in the sub-cohort with a small number of preoperative ADs and small VFA (100% and 16.7%, respectively) were better than those in the sub-cohort with a large number of preoperative ADs and large VFA (5.3% and 100%, respectively). In Japanese patients with severe obesity, the number of preoperative ADs and VFA were correlated with HTN remission and recurrence post-LSG. Stratification, by combining the number of preoperative ADs and VFA, may be useful in predicting HTN remission and recurrence.

Dataset Information

Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis.

Publications

Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets