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

Abstract

Background and aimsGalanin 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.MethodsThe 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 CCl4 for 7 weeks. The underlying mechanism was also studied in vitro on murine macrophage cells (J774A.1 and RAW264.7).ResultsGalanin 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 CCl4. In vitro, 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.ConclusionGalanin ameliorates liver inflammation and fibrosis in mice, potentially by modifying macrophage inflammatory phenotype and activating AMPK/ACC signaling.

Fatty acid metabolism disorders and potential therapeutic traditional Chinese medicines in cardiovascular diseases

“…Since malonyl‐CoA is acknowledged to be a negative regulator of CPT‐1. Hence, AMPK could effectively attenuate the inhibition of CPT‐1 and promote fatty acid oxidation (He et al, 2023; Lepropre et al, 2018). In addition, AMPK accelerates fatty acid metabolism by increasing fatty acid uptake via enhancing the expression of FAT/CD36 and FABP (Luiken et al, 2018; Wu et al, 2020).…”