Next Article in Journal
Mitochondrial Dynamics in Placenta-Derived Mesenchymal Stem Cells Regulate the Invasion Activity of Trophoblast
Next Article in Special Issue
From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis
Previous Article in Journal
In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation
Previous Article in Special Issue
miR-29a Modulates GSK3β/SIRT1-Linked Mitochondrial Proteostatic Stress to Ameliorate Mouse Non-Alcoholic Steatohepatitis
Open AccessArticle

IL-18 But Not IL-1 Signaling Is Pivotal for the Initiation of Liver Injury in Murine Non-Alcoholic Fatty Liver Disease

1
Department of Medicine II, University Hospital, LMU Munich, 81377 Munich, Germany
2
Institute of Pathology, Faculty of Medicine, LMU Munich, 80337 Munich, Germany
3
Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, 81377 Munich, Germany
4
Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany
5
Division of Gastroenterology, Endocrinology, Infectiology and Metabolism, University Hospital Giessen and Marburg, Campus Marburg, Philipps University Marburg, 35043 Marburg, Germany
6
Institute of Laboratory Medicine, University Hospital, LMU Munich, 81377 Munich, Germany
7
Department of Medicine I, Hospital Barmherzige Brüder, 80639 Munich, Germany
8
Division of Clinical Pharmacology, University Hospital, LMU Munich, 80336 Munich, Germany
9
Institute of Toxicology and Environmental Hygiene, Technical University Munich, School of Medicine, 80802 Munich, Germany
10
Division of Hepatology, University Hospital Würzburg, 97080 Würzburg, Germany
11
Transplantation Center Munich, University Hospital, LMU Munich, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8602; https://doi.org/10.3390/ijms21228602
Received: 15 October 2020 / Revised: 6 November 2020 / Accepted: 9 November 2020 / Published: 14 November 2020
(This article belongs to the Special Issue Pathophysiology of Chronic Liver Disease Development)
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, Il-18r−/−- but not Il-1r−/− mice were protected from early liver damage, possibly due to silencing of the pro-inflammatory gene expression pattern. Our study identified NLRP3 activation and IL-18R-dependent signaling as potential modulators of early liver damage in NAFLD, preceding development of histologic NASH. View Full-Text
Keywords: NAFLD; Western diet; NLRP3; inflammasome; interleukin 1; interleukin 18; NASH; ALiOS NAFLD; Western diet; NLRP3; inflammasome; interleukin 1; interleukin 18; NASH; ALiOS
Show Figures

Figure 1

MDPI and ACS Style

Hohenester, S.; Kanitz, V.; Schiergens, T.; Einer, C.; Nagel, J.; Wimmer, R.; Reiter, F.P.; Gerbes, A.L.; De Toni, E.N.; Bauer, C.; Holdt, L.; Mayr, D.; Rust, C.; Schnurr, M.; Zischka, H.; Geier, A.; Denk, G. IL-18 But Not IL-1 Signaling Is Pivotal for the Initiation of Liver Injury in Murine Non-Alcoholic Fatty Liver Disease. Int. J. Mol. Sci. 2020, 21, 8602. https://doi.org/10.3390/ijms21228602

AMA Style

Hohenester S, Kanitz V, Schiergens T, Einer C, Nagel J, Wimmer R, Reiter FP, Gerbes AL, De Toni EN, Bauer C, Holdt L, Mayr D, Rust C, Schnurr M, Zischka H, Geier A, Denk G. IL-18 But Not IL-1 Signaling Is Pivotal for the Initiation of Liver Injury in Murine Non-Alcoholic Fatty Liver Disease. International Journal of Molecular Sciences. 2020; 21(22):8602. https://doi.org/10.3390/ijms21228602

Chicago/Turabian Style

Hohenester, Simon; Kanitz, Veronika; Schiergens, Tobias; Einer, Claudia; Nagel, Jutta; Wimmer, Ralf; Reiter, Florian P.; Gerbes, Alexander L.; De Toni, Enrico N.; Bauer, Christian; Holdt, Lesca; Mayr, Doris; Rust, Christian; Schnurr, Max; Zischka, Hans; Geier, Andreas; Denk, Gerald. 2020. "IL-18 But Not IL-1 Signaling Is Pivotal for the Initiation of Liver Injury in Murine Non-Alcoholic Fatty Liver Disease" Int. J. Mol. Sci. 21, no. 22: 8602. https://doi.org/10.3390/ijms21228602

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop