IL-18 but Not IL-1 Signaling Is Pivotal for the Initiation of Liver Injury in Murine Non-Alcoholic Fatty Liver Disease.
ALiOS
NAFLD
NASH
NLRP3
Western diet
inflammasome
interleukin 1
interleukin 18
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
14 Nov 2020
14 Nov 2020
Historique:
received:
15
10
2020
revised:
06
11
2020
accepted:
09
11
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
5
3
2021
Statut:
epublish
Résumé
Non-alcoholic fatty liver disease (NAFLD) is rising in prevalence, and a better pathophysiologic understanding of the transition to its inflammatory phenotype (NASH) is key to the development of effective therapies. To evaluate the contribution of the NLRP3 inflammasome and its downstream effectors IL-1 and IL-18 in this process, we applied the true-to-life "American lifestyle-induced obesity syndrome" (ALiOS) diet mouse model. Development of obesity, fatty liver and liver damage was investigated in mice fed for 24 weeks according to the ALiOS protocol. Lipidomic changes in mouse livers were compared to human NAFLD samples. Receptor knockout mice for IL-1 and IL-18 were used to dissect the impact of downstream signals of inflammasome activity on the development of NAFLD. The ALiOS diet induced obesity and liver steatosis. The lipidomic changes closely mimicked changes in human NAFLD. A pro-inflammatory gene expression pattern in liver tissue and increased serum liver transaminases indicated early liver damage in the absence of histological evidence of NASH. Mechanistically,
Identifiants
pubmed: 33202693
pii: ijms21228602
doi: 10.3390/ijms21228602
pmc: PMC7696705
pii:
doi:
Substances chimiques
Interleukin-1
0
Interleukin-18
0
Receptors, Interleukin-1
0
Receptors, Interleukin-18
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : HO4460/3-1
Organisme : Medizinischen Fakultät, Ludwig-Maximilians-Universität München
ID : FöFoLe #905
Références
Nature. 2012 Feb 01;482(7384):179-85
pubmed: 22297845
Nat Rev Gastroenterol Hepatol. 2019 Jun;16(6):377-386
pubmed: 31024089
Can J Gastroenterol Hepatol. 2018 Apr 26;2018:3870454
pubmed: 29854715
Hepatology. 2016 Jul;64(1):73-84
pubmed: 26707365
Hepatology. 2005 Jun;41(6):1313-21
pubmed: 15915461
Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G987-95
pubmed: 18772365
Am J Physiol Gastrointest Liver Physiol. 2018 Sep 1;315(3):G329-G338
pubmed: 29878845
Nat Immunol. 2011 May;12(5):408-15
pubmed: 21478880
Cell Tissue Bank. 2003;4(1):49-56
pubmed: 15256870
Chem Biol Interact. 2019 Feb 25;300:56-62
pubmed: 30639268
Hepatology. 2014 Apr;59(4):1393-405
pubmed: 24254368
Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):686-90
pubmed: 24042449
Arch Pharm Res. 2016 Nov;39(11):1503-1518
pubmed: 27600432
Gut. 2020 Mar;69(3):564-568
pubmed: 31366455
Cell Mol Gastroenterol Hepatol. 2019;7(3):571-596
pubmed: 30586623
Annu Rev Cell Dev Biol. 2012;28:137-61
pubmed: 22974247
J Hepatol. 2011 Nov;55(5):1086-94
pubmed: 21354232
Gastroenterology. 2010 Jul;139(1):323-34.e7
pubmed: 20347818
J Hepatol. 2016 Jun;64(6):1388-402
pubmed: 27062661
PLoS One. 2016 Mar 01;11(3):e0150018
pubmed: 26930607
Sci Rep. 2019 Apr 30;9(1):6668
pubmed: 31040374
Data Brief. 2017 Sep 18;15:163-169
pubmed: 29034285
J Biol Chem. 1957 May;226(1):497-509
pubmed: 13428781
Nutrients. 2019 Nov 24;11(12):
pubmed: 31771244
Cell. 2004 May 28;117(5):561-74
pubmed: 15163405
World J Hepatol. 2016 Mar 18;8(8):401-10
pubmed: 27004088
Diabetes. 2010 Dec;59(12):3181-91
pubmed: 20858684
Hepatology. 2011 Jul;54(1):133-44
pubmed: 21488066
Arch Toxicol. 2017 Apr;91(4):1545-1563
pubmed: 27995280
J Sports Med Phys Fitness. 2019 Aug;59(8):1376-1388
pubmed: 30758165
PLoS One. 2014 Dec 23;9(12):e115922
pubmed: 25535951
Gastroenterology. 2012 Nov;143(5):1158-1172
pubmed: 22982943
Gut. 2018 Apr;67(4):746-756
pubmed: 28053052
Mitochondrion. 2018 May;40:1-12
pubmed: 28935446
PLoS One. 2014 Aug 07;9(8):e104220
pubmed: 25101998
Clin Chim Acta. 1980 Jun 10;104(2):161-7
pubmed: 7389130
Methods Mol Biol. 2015;1295:75-86
pubmed: 25820715
Hepatology. 2012 Nov;56(5):1751-9
pubmed: 22707395
Liver Int. 2015 Feb;35(2):582-90
pubmed: 25219574