Koehler, Nikolai and Hoering, Marcus and Czepukojc, Beate and Rose, Tim Daniel and Buechler, Christa and Kroehler, Tarek and Haybaeck, Johannes and Liebisch, Gerhard and Pauling, Josch K. and Kessler, Sonja M. and Kiemer, Alexandra K. (2022) Kupffer cells are protective in alcoholic steatosis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1868 (6): 166398. ISSN 0925-4439, 1879-260X
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOPLASMIC-RETICULUM STRESS; HIGH-THROUGHPUT QUANTIFICATION; LIVER-DISEASE PATHOGENESIS; ADIPOSE-TISSUE; INSULIN-RESISTANCE; HEPATIC STEATOSIS; LEUCINE-ZIPPER; ETHANOL; INJURY; ACID; Lieber-DeCarli diet; Lipidomics; Macrophages; Phospholipids; Sphingolipids; Bi-clustering; Louvain communities |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2024 11:20 |
| Last Modified: | 29 Jan 2024 13:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58052 |
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