PUBLICATION

A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity

Authors
Dapueto, R., Rodriguez-Duarte, J., Galliussi, G., Kamaid, A., Bresque, M., Batthyány, C., López, G.V., Escande, C.
ID
ZDB-PUB-201223-13
Date
2020
Source
Redox Biology   39: 101833 (Journal)
Registered Authors
Keywords
Diet induced obesity, Glucose intolerance, Inflammasomes, Inflammation related diseases, Nitroalkenes
MeSH Terms
  • Mice
  • Glucose Intolerance*/drug therapy
  • Obesity/drug therapy
  • Inflammasomes
  • Inflammation/drug therapy
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Vitamin E
  • Zebrafish
  • Diabetes Mellitus, Type 2*
  • Lipopolysaccharides
  • Animals
  • Interleukin-1beta
(all 12)
PubMed
33352465 Full text @ Redox Biol.
Abstract
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.
Genes / Markers
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i114Tgtransection: caudal finProtruding-mouth
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    i114Tg
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    GFPEFGGFP
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    Citation
    Dapueto, R., Rodriguez-Duarte, J., Galliussi, G., Kamaid, A., Bresque, M., Batthyány, C., López, G.V., Escande, C. (2020) A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity. Redox Biology. 39:101833.