Please use this identifier to cite or link to this item: doi:10.22028/D291-37441
Title: Kupffer cells are protective in alcoholic steatosis
Author(s): Köhler, Nikolai
Höring, Marcus
Czepukojc, Beate
Rose, Tim Daniel
Buechler, Christa
Kröhler, Tarek
Haybaeck, Johannes
Liebisch, Gerhard
Pauling, Josch K.
Kessler, Sonja M.
Kiemer, Alexandra K.
Language: English
Title: Biochimica et Biophysica Acta. Molecular Basis of Disease
Volume: 1868
Issue: 6
Publisher/Platform: Elsevier
Year of Publication: 2022
Free key words: Lieber-DeCarli diet
Louvain communities
DDC notations: 500 Science
Publikation type: Journal Article
Abstract: Massive accumulation of lipids is a characteristic of alcoholic liver disease. Excess of hepatic fat activates Kupffer cells (KCs), which affect disease progression. Yet, KCs contribute to the resolution and advancement of liver injury. Aim of the present study was to evaluate the effect of KC depletion on markers of liver injury and the hepatic lipidome in liver steatosis (Lieber-DeCarli diet, LDC, female mice, mixed C57BL/6J and DBA/2J background). LDC increased the number of dead hepatocytes without changing the mRNA levels of inflammatory cytokines in the liver. Animals fed LDC accumulated elevated levels of almost all lipid classes. KC ablation normalized phosphatidylcholine and phosphatidylinositol levels in LDC livers, but had no effect in the controls. A modest decline of trigylceride and diglyceride levels upon KC loss was observed in both groups. Serum aminotransferases and hepatic ceramide were elevated in all animals upon KC depletion, and in particular, cytotoxic very long-chain ceramides increased in the LDC livers. Meta-biclustering revealed that eight lipid species occurred in more than 40% of the biclusters, and four of them were very long-chain ceramides. KC loss was further associated with excess free cholesterol levels in LDC livers. Expression of inflammatory cytokines did, however, not increase in parallel. In summary, the current study described a function of KCs in hepatic ceramide and cholesterol metabolism in an animal model of LDC liver steatosis. High abundance of cytotoxic ceramides and free cholesterol predispose the liver to disease progression suggesting a protective role of KCs in alcoholic liver diseases.
DOI of the first publication: 10.1016/j.bbadis.2022.166398
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-374413
ISSN: 0925-4439
Date of registration: 29-Sep-2022
Description of the related object: Supplementary data
Related object:
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Alexandra K. Kiemer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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