AUTHOR=He Lingnan , Huang Chao , Wang Hui , Yang Naibin , Zhang Jianbin , Xu Leiming , Gu Ting , Li Zhenghong , Chen Yuanwen 

TITLE=Galanin ameliorates liver inflammation and fibrosis in mice by activating AMPK/ACC signaling and modifying macrophage inflammatory phenotype

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1161676

DOI=10.3389/fimmu.2023.1161676

ISSN=1664-3224

ABSTRACT=<sec><title>Background and aims</title><p>Galanin is a naturally occurring peptide that plays a critical role in regulating inflammation and energy metabolism, with expression in the liver. The exact involvement of galanin in non-alcoholic fatty liver disease and related fibrosis remains controversial.</p></sec><sec><title>Methods</title><p>The effects of subcutaneously administered galanin were studied in mice with non-alcoholic steatohepatitis (NASH) induced by a high-fat and high-cholesterol diet for 8 weeks, and in mice with liver fibrosis induced by CCl<sub>4</sub> for 7 weeks. The underlying mechanism was also studied <italic>in vitro</italic> on murine macrophage cells (J774A.1 and RAW264.7).</p></sec><sec><title>Results</title><p>Galanin reduced inflammation, CD68-positive cell count, MCP-1 level, and mRNA levels of inflammation-related genes in the liver of NASH mice. It also mitigated liver injury and fibrosis caused by CCl<sub>4</sub>. <italic>In vitro</italic>, galanin had anti-inflammatory effects on murine macrophages, including reduced phagocytosis and intracellular reactive oxygen species (ROS). Galanin also activated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling.</p></sec><sec><title>Conclusion</title><p>Galanin ameliorates liver inflammation and fibrosis in mice, potentially by modifying macrophage inflammatory phenotype and activating AMPK/ACC signaling.</p></sec>