Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis

Pohl, Rebekka and Feder, Susanne and Haberl, Elisabeth M. and Rein-Fischboeck, Lisa and Weiss, Thomas S. and Spirk, Marlen and Bruckmann, Astrid and McMullen, Nichole and Sinal, Christopher J. and Buechler, Christa (2022) Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis. BIOMEDICINES, 10 (1): 132. ISSN , 2227-9059

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Abstract

Non-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH. Therefore, mice were infected with adeno-associated virus 8 to direct hepatic overexpression of prochemerin in a methionine-choline deficient dietary model of NASH. At the end of the study, hepatic and serum chemerin were higher in the chemerin-expressing mice. These animals had less hepatic oxidative stress, F4/80 and CC-chemokine ligand 2 (CCL2) protein, and mRNA levels of inflammatory genes than the respective control animals. In order to identify the underlying mechanisms, prochemerin was expressed in hepatocytes and the hepatic stellate cells, LX-2. Here, chemerin had no effect on cell viability, production of inflammatory, or pro-fibrotic factors. Notably, cultivation of human peripheral blood mononuclear cells (PBMCs) in the supernatant of Huh7 cells overexpressing chemerin reduced CCL2, interleukin-6, and osteopontin levels in cell media. CCL2 was also low in RAW264.7 cells exposed to Hepa1-6 cell produced chemerin. In summary, the current study showed that prochemerin overexpression had little effect on hepatocytes and hepatic stellate cells. Of note, hepatocyte-produced chemerin deactivated PBMCs and protected against inflammation in experimental NASH.

Item Type: Article
Uncontrolled Keywords: MESSENGER-RNA EXPRESSION; HEPATIC STELLATE CELLS; INSULIN-RESISTANCE; ANIMAL-MODELS; EX-VIVO; ACTIVATION; MICE; ADIPONECTIN; ADIPOKINE; OBESITY; peripheral blood mononuclear cells; chemerin activity; hepatic inflammation; hepatic stellate cells
Subjects: 500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Kinder- und Jugendmedizin
Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Nov 2023 13:45
Last Modified: 07 Nov 2023 13:45
URI: https://pred.uni-regensburg.de/id/eprint/56693

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