Pohl, Rebekka and Eichelberger, Laura and Feder, Susanne and Haberl, Elisabeth M. and Rein-Fischboeck, Lisa and McMullen, Nichole and Sinal, Christopher J. and Bruckmann, Astrid and Weiss, Thomas S. and Beck, Michael and Horing, Marcus and Krautbauer, Sabrina and Liebisch, Gerhard and Wiest, Reiner and Wanninger, Josef and Buechler, Christa (2022) Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis. MOLECULAR AND CELLULAR BIOCHEMISTRY, 477 (8). pp. 2059-2071. ISSN 0300-8177, 1573-4919
Full text not available from this repository. (Request a copy)Abstract
Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described. Here, the effect of hepatocyte expressed muChem-156, a highly active murine chemerin isoform, was studied in the methionine-choline deficient dietary model of NASH. Mice overexpressing muChem-156 had higher hepatic chemerin protein. Serum chemerin levels and the capability of serum to activate the chemerin receptors was unchanged showing that the liver did not release active chemerin. Notably, activation of the chemerin receptors by hepatic vein blood did not increase in parallel to total chemerin protein in patients with liver cirrhosis. In experimental NASH, muChem-156 had no effect on liver lipids. Accordingly, overexpression of active chemerin in hepatocytes or treatment of hepatocytes with recombinant chemerin did not affect cellular triglyceride and cholesterol levels. Importantly, overexpression of muChem-156 in the murine liver did not change the hepatic expression of inflammatory and profibrotic genes. The downstream targets of chemerin such as p38 kinase were neither activated in the liver of muChem-156 producing mice nor in HepG2, Huh7 and Hepa1-6 cells overexpressing this isoform. Recombinant chemerin had no effect on global gene expression of primary human hepatocytes and hepatic stellate cells within 24 h of incubation. Phosphorylation of p38 kinase was, however, increased upon short-time incubation of HepG2 cells with chemerin. These findings show that muChem-156 overexpression in hepatocytes does not protect from liver steatosis and inflammation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SERUM CHEMERIN; ANIMAL-MODELS; LIVER; ADIPOKINE; INFLAMMATION; OBESITY; CMKLR1; MICE; GPR1; STAT3; p38; Triglycerides; Hepatic stellate cells; Gene expression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Kinder- und Jugendmedizin Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jan 2024 11:24 |
| Last Modified: | 29 Jan 2024 12:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56757 |
Actions (login required)
 |
View Item |
