Liver repercussions of defective gut surveillance

Irvine, Katharine M., Schroder, Elizabeth E. and Powell, Elizabeth E. (2012) Liver repercussions of defective gut surveillance. Hepatology, 56 3: 1174-1177. doi:10.1002/hep.25944

Author Irvine, Katharine M.
Schroder, Elizabeth E.
Powell, Elizabeth E.
Title Liver repercussions of defective gut surveillance
Journal name Hepatology   Check publisher's open access policy
ISSN 0270-9139
Publication date 2012-09
Sub-type Article (original research)
DOI 10.1002/hep.25944
Volume 56
Issue 3
Start page 1174
End page 1177
Total pages 4
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2013
Language eng
Formatted abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of
chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation
(non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the
causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes
and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated
changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation
through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour- necrosis factor
(TNF)-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wildtype
mice results in exacerbation of hepatic steatosis and obesity.  Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple
metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 31 Aug 2012, 14:28:15 EST by Dr Kate Schroder on behalf of School of Chemistry & Molecular Biosciences