Insulin resistance and liver histopathology in metabolically unhealthy subjects do not correlate with the hepatic abundance of NLRP3 inflammasome nor circulating IL-1β levels

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dc.catalogadordfo
dc.contributor.authorQuezada Sanhueza, Nicolás
dc.contributor.authorValencia, Ilse
dc.contributor.authorTorres, Javiera
dc.contributor.authorMaturana, Gregorio
dc.contributor.authorCerda, Jaime
dc.contributor.authorArab Verdugo, Juan Pablo
dc.contributor.authorFuentes, Juan José
dc.contributor.authorPinto, Claudio
dc.contributor.authorTuriel, Dannae
dc.contributor.authorCortes Mora, Víctor Antonio
dc.date.accessioned2024-01-26T14:04:44Z
dc.date.available2024-01-26T14:04:44Z
dc.date.issued2021
dc.description.abstractIntroduction Systemic chronic low-grade inflammation has been linked to insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). NOD-like receptor protein 3 (NLRP3) inflammasome and its final product, interleukin (IL)-1 beta, exert detrimental effects on insulin sensitivity and promote liver inflammation in murine models. Evidence linking hepatic NLRP3 inflammasome, systemic IR and NASH has been scarcely explored in humans. Herein, we correlated the hepatic abundance of NLRP3 inflammasome components and IR and NASH in humans.||Research design and methods Metabolically healthy (MH) (n=11) and metabolically unhealthy (MUH) (metabolic syndrome, n=21, and type 2 diabetes, n=14) subjects were recruited. Insulin sensitivity (homeostatic model assessment of IR (HOMA-IR) and Oral Glucose Sensitivity (OGIS(120))), glycemic (glycated hemoglobin), and lipid parameters were determined by standard methods. Plasma cytokines were quantified by Magpix. Hepatic NLRP3 inflammasome components were determined at the mRNA and protein levels by reverse transcription-quantitative PCR and western blot, respectively. Liver damage was assessed by histological analysis (Non-alcoholic Fatty Liver Disease Activity Score (NAS) and Steatosis, Inflammatory Activity, and Fibrosis (SAF) scores). IR and liver histopathology were correlated with NLRP3 inflammasome components as well as with liver and plasma IL-1 beta levels.||Results Body Mass Index, waist circumference, and arterial hypertension frequency were significantly higher in MUH subjects. These patients also had increased high-sensitivity C reactive protein levels compared with MH subjects. No differences in the plasma levels of IL-1 beta nor the hepatic content of Nlrp3, apoptosis-associated speck-like (Asc), Caspase-1, and IL-1 beta were detected between MUH and MH individuals. MUH subjects had significantly higher NAS and SAF scores, indicating more severe liver damage. However, histological severity did not correlate with the hepatic content of NLRP3 inflammasome components nor IL-1 beta levels.||Conclusion Our results suggest that NLRP3 inflammasome activation is linked neither to IR nor to the inflammatory status of the liver in MUH patients.
dc.fuente.origenConveris
dc.identifier.doi10.1136/bmjdrc-2020-001975
dc.identifier.issn2052-4897
dc.identifier.scopusidSCOPUS_ID:2-s2.0-85105317786
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80978
dc.information.autorucEscuela de Medicina; Quezada Sanhueza Nicolas Fernando; S/I; 127224
dc.information.autorucEscuela de Medicina; Cerda Lorca Jaime Rodrigo; 0000-0003-3463-8304; 3935
dc.information.autorucEscuela de Medicina; Arab Verdugo Juan Pablo; 0000-0002-8561-396X; 132745
dc.information.autorucEscuela de Medicina; Turiel Araya Dannae De Las Mercedes; S/I; 93415
dc.information.autorucEscuela de Medicina; Cortes Mora Victor Antonio; 0000-0002-1658-0965; 7576
dc.language.isoen
dc.nota.accesoContenido parcial
dc.revistaBMJ Open Diabetes Research & Care
dc.rightsacceso restringido
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleInsulin resistance and liver histopathology in metabolically unhealthy subjects do not correlate with the hepatic abundance of NLRP3 inflammasome nor circulating IL-1β levels
dc.typeartículo
sipa.codpersvinculados127224
sipa.codpersvinculados3935
sipa.codpersvinculados132745
sipa.codpersvinculados93415
sipa.codpersvinculados7576
sipa.trazabilidadConveris;20-07-2021
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