RT Journal Article
T1 Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis.
A1 Cabre, Noemi
A1 Luciano-Mateo, Fedra
A1 Chapski, Douglas J
A1 Baiges-Gaya, Gerard
A1 Fernandez-Arroyo, Salvador
A1 Hernandez-Aguilera, Anna
A1 Castañe, Helena
A1 Rodriguez-Tomas, Elisabet
A1 Paris, Marta
A1 Sabench, Fatima
A1 Castillo, Daniel Del
A1 Del Bas, Josep M
A1 Tome, Mercedes
A1 Bodineau, Clement
A1 Sola-Garcia, Alejandro
A1 Lopez-Miranda, Jose
A1 Martin-Montalvo, Alejandro
A1 Duran, Raul V
A1 Vondriska, Thomas M
A1 Rosa-Garrido, Manuel
A1 Camps, Jordi
A1 Menendez, Javier A
A1 Joven, Jorge
K1 DNA methylation
K1 Bariatric surgery
K1 Energy metabolism
K1 Epigenetics
K1 Functional studies
K1 Glutaminolysis
K1 Multi-omics approach
AB 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.
PB MDPI
YR 2022
FD 2022-07-13
LK http://hdl.handle.net/10668/21173
UL http://hdl.handle.net/10668/21173
LA en
NO Cabré N, Luciano-Mateo F, Chapski DJ, Baiges-Gaya G, Fernández-Arroyo S, Hernández-Aguilera A, et al. Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis. Int J Mol Sci. 2022 Jul 15;23(14):7830
DS RISalud
RD Apr 8, 2025