A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity
Chronic metabolic diseases, like obesity, type II diabetes and atherosclerosis often involve a low-grade and sterile systemic inflammatory state, in which activation of the pro-inflammatory transcription factor NF-kB and the NLRP3 inflammasome play a major role. It is well established that genetic i...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2021-02-01
|
Series: | Redox Biology |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720310387 |
id |
doaj-fd342c50fe4445279342c16afc73566b |
---|---|
record_format |
Article |
spelling |
doaj-fd342c50fe4445279342c16afc73566b2021-01-14T04:17:14ZengElsevierRedox Biology2213-23172021-02-0139101833A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesityRosina Dapueto0Jorge Rodriguez-Duarte1Germán Galliussi2Andrés Kamaid3Mariana Bresque4Carlos Batthyány5Gloria V. López6Carlos Escande7Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay; Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, UruguayLaboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, UruguayLaboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, UruguayLaboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, UruguayLaboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, UruguayLaboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay; Corresponding author.Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay; Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Uruguay; Corresponding author. Laboratory of Vascular Biology and Drug Development, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay.Laboratory of Metabolic Diseases and Aging, INDICYO Program, Institut Pasteur de Montevideo, Montevideo, Uruguay; Corresponding author.Chronic metabolic diseases, like obesity, type II diabetes and atherosclerosis often involve a low-grade and sterile systemic inflammatory state, in which activation of the pro-inflammatory transcription factor NF-kB and the NLRP3 inflammasome play a major role. It is well established that genetic inhibition of the NLRP3 inflammasome ameliorates acute and chronic inflammation. Indeed, accumulating experimental evidences in murine models and also in humans suggest that inhibition of the NLRP3 inflammasome might be a suitable approach to tackle the deleterious effects of chronic metabolic diseases. In this work, we explored our previously synthesized nitroalkene-Trolox™ derivative named NATx0, as a non-conventional anti-inflammatory strategy to treat chronic inflammatory diseases, such as obesity-induced glucose intolerance. We found that NATx0 inhibited NF-kB nuclear translocation and pro-inflammatory gene expression in macrophages in vitro. In addition, treatment with NATx0 prevented NLRP3 inflammasome activation after LPS/ATP stimulation in macrophages in vitro. When tested acutely in vivo, NATx0 inhibited neutrophil recruitment in zebrafish larvae, and also diminished IL-1β production after LPS challenge in mice. Finally, when NATx0 was administered chronically to diet-induced obese mice, it decreased muscle tissue inflammation and glucose intolerance, leading to improved glucose homeostasis. In conclusion, we propose that this novel nitroalkene-Trolox derivative is a suitable tool to tackle acute and chronic inflammation in vitro and in vivo mainly due to inhibition of NF-kB/NLRP3 activation.http://www.sciencedirect.com/science/article/pii/S2213231720310387Inflammation related diseasesInflammasomesNitroalkenesDiet induced obesityGlucose intolerance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rosina Dapueto Jorge Rodriguez-Duarte Germán Galliussi Andrés Kamaid Mariana Bresque Carlos Batthyány Gloria V. López Carlos Escande |
spellingShingle |
Rosina Dapueto Jorge Rodriguez-Duarte Germán Galliussi Andrés Kamaid Mariana Bresque Carlos Batthyány Gloria V. López Carlos Escande A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity Redox Biology Inflammation related diseases Inflammasomes Nitroalkenes Diet induced obesity Glucose intolerance |
author_facet |
Rosina Dapueto Jorge Rodriguez-Duarte Germán Galliussi Andrés Kamaid Mariana Bresque Carlos Batthyány Gloria V. López Carlos Escande |
author_sort |
Rosina Dapueto |
title |
A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity |
title_short |
A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity |
title_full |
A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity |
title_fullStr |
A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity |
title_full_unstemmed |
A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity |
title_sort |
novel nitroalkene vitamin e analogue inhibits the nlrp3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2021-02-01 |
description |
Chronic metabolic diseases, like obesity, type II diabetes and atherosclerosis often involve a low-grade and sterile systemic inflammatory state, in which activation of the pro-inflammatory transcription factor NF-kB and the NLRP3 inflammasome play a major role. It is well established that genetic inhibition of the NLRP3 inflammasome ameliorates acute and chronic inflammation. Indeed, accumulating experimental evidences in murine models and also in humans suggest that inhibition of the NLRP3 inflammasome might be a suitable approach to tackle the deleterious effects of chronic metabolic diseases. In this work, we explored our previously synthesized nitroalkene-Trolox™ derivative named NATx0, as a non-conventional anti-inflammatory strategy to treat chronic inflammatory diseases, such as obesity-induced glucose intolerance. We found that NATx0 inhibited NF-kB nuclear translocation and pro-inflammatory gene expression in macrophages in vitro. In addition, treatment with NATx0 prevented NLRP3 inflammasome activation after LPS/ATP stimulation in macrophages in vitro. When tested acutely in vivo, NATx0 inhibited neutrophil recruitment in zebrafish larvae, and also diminished IL-1β production after LPS challenge in mice. Finally, when NATx0 was administered chronically to diet-induced obese mice, it decreased muscle tissue inflammation and glucose intolerance, leading to improved glucose homeostasis. In conclusion, we propose that this novel nitroalkene-Trolox derivative is a suitable tool to tackle acute and chronic inflammation in vitro and in vivo mainly due to inhibition of NF-kB/NLRP3 activation. |
topic |
Inflammation related diseases Inflammasomes Nitroalkenes Diet induced obesity Glucose intolerance |
url |
http://www.sciencedirect.com/science/article/pii/S2213231720310387 |
work_keys_str_mv |
AT rosinadapueto anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT jorgerodriguezduarte anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT germangalliussi anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT andreskamaid anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT marianabresque anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT carlosbatthyany anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT gloriavlopez anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT carlosescande anovelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT rosinadapueto novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT jorgerodriguezduarte novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT germangalliussi novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT andreskamaid novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT marianabresque novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT carlosbatthyany novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT gloriavlopez novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity AT carlosescande novelnitroalkenevitamineanalogueinhibitsthenlrp3inflammasomeandprotectsagainstinflammationandglucoseintolerancetriggeredbyobesity |
_version_ |
1724338518232137728 |