NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling

The NLRP3-IL-1β pathway plays an important role in adipose tissue (AT)-induced inflammation and the development of obesity-associated comorbidities. We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extrace...

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Veröffentlicht in:	Cellular & molecular immunology 2021-04, Vol.18 (4), p.1045-1057
Hauptverfasser:	Unamuno, Xabier, Gómez-Ambrosi, Javier, Ramírez, Beatriz, Rodríguez, Amaia, Becerril, Sara, Valentí, Víctor, Moncada, Rafael, Silva, Camilo, Salvador, Javier, Frühbeck, Gema, Catalán, Victoria
Format:	Artikel
Sprache:	eng
Schlagworte:	631/250/127/1213 631/250/256/2177 Adipocytes Adipose tissue Adipose Tissue - immunology Adipose Tissue - metabolism Adipose Tissue - pathology Adult Antibodies Biomedical and Life Sciences Biomedicine Case-Control Studies Collagen (type I) Diabetes Mellitus, Type 2 - immunology Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - pathology Extracellular matrix Extracellular Matrix - immunology Extracellular Matrix - metabolism Extracellular Matrix - pathology Female Fibrosis Gelatinase A Gene expression Humans Hypoxia IL-1β Immunology Inflammasomes Inflammasomes - immunology Inflammation Inflammation - immunology Inflammation - metabolism Inflammation - pathology Interleukin 1 Interleukin 18 Interleukin 6 Interleukin 8 Interleukin-18 - genetics Interleukin-18 - metabolism Interleukin-1beta - genetics Interleukin-1beta - metabolism Lipopolysaccharides Male Medical Microbiology Microbiology Monocyte chemoattractant protein 1 NLR Family, Pyrin Domain-Containing 3 Protein - genetics NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Non-alcoholic Fatty Liver Disease - immunology Non-alcoholic Fatty Liver Disease - pathology Obesity Obesity - complications Signal Transduction siRNA TLR4 protein Toll-like receptors Tumor necrosis factor Vaccine Young Adult
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Zusammenfassung:	The NLRP3-IL-1β pathway plays an important role in adipose tissue (AT)-induced inflammation and the development of obesity-associated comorbidities. We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix (ECM) remodeling. Samples obtained from 98 subjects were used in a case−control study. The expression of different components of the inflammasome as well as their main effectors and inflammation- and ECM remodeling-related genes were analyzed. The impact of blocking NLRP3 using siRNA in lipopolysaccharide (LPS)-mediated inflammation and ECM remodeling signaling pathways was evaluated. We demonstrated that obesity ( P
ISSN:	1672-7681 2042-0226
DOI:	10.1038/s41423-019-0296-z