Knockdown of GBP5 alleviates lipid accumulation and inflammation in alcoholic fatty liver through inhibition of NF-κB pathway in mice

Abstract

Alcoholic liver disease (ALD) is a global liver disease that manifests in a variety of forms, including alcoholic hepatitis, liver inflammation, fatty liver, and liver cirrhosis. One of the early stages of ALD is alcoholic fatty liver (AFL) disease, which is primarily characterized by the accumulation of lipids and inflammation in hepatocytes. Guanylate binding protein 5 (GBP5) has been investigated for its involvement in disease progression. The regulatory effects of GBP5 on the progression of AFL disease are still not well understood. This study aims to investigate the impact of GBP5 on AFL progression and its underlying mechanism of action. To achieve this, gene expression was evaluated using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) methods. Lipid accumulation was confirmed using the Oil Red O staining assay, while the levels of Triglyceride (TG), aspartate aminotransferases (AST), and alanine aminotransferases (ALT) were measured using commercial kits. The levels of inflammatory cytokines were assessed using enzyme-linked immuno sorbent assay (ELISA) assay. Finally, cell apoptosis was evaluated using flow cytometry. Cell apoptosis was evaluated through flow cytometry. Our work demonstrated that GBP5 expression was up-regulated in the Ethyl Alcohol (EtOH) group. Additionally, lipid accumulation was increased after EtOH inducement, but this change was attenuated by silencing GBP5. Silencing of GBP5 reduced EtOH-mediated inflammation and cell apoptosis. Finally, it was discovered that knockdown of GBP5 retarded the EtOH-stimulated nuclear factor kappa-B (NF-κB) pathway. Knockdown of GBP5 alleviated lipid accumulation and inflammation in AFL through inhibition of NF-κB pathway. This finding suggested that GBP5 may be a useful bio-target for AFL treatment.