TY  - JOUR
A1  - Dorochow, Erika
A1  - Kraus, Nico
A1  - Chenaux-Repond, Nicolas
A1  - Pierre, Sandra
A1  - Kolbinger, Anja
A1  - Geisslinger, Gerd
A1  - Ortiz, Cristina
A1  - Welsch, Christoph
A1  - Trebicka, Jonel
A1  - Gurke, Robert
A1  - Hahnefeld, Lisa Katharina
A1  - Klein, Sabine
A1  - Scholich, Klaus
T1  - Differential lipidomics, metabolomics and immunological analysis of alcoholic and non-alcoholic steatohepatitis in mice
T2  - International journal of molecular sciences
N2  - Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses.
KW  - non-alcoholic fatty liver disease
KW  - alcoholic fatty liver disease
KW  - lipid droplets
KW  - metabolomics
KW  - lipidomics
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/78728
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-787280
SN  - 1422-0067
VL  - 24
IS  - 12
PB  - MDPI
CY  - Basel
ER  -