FABP4 deficiency ameliorates alcoholic steatohepatitis in mice via inhibition of p53 signaling pathway

Abstract Fatty acid-binding protein 4 (FABP4) plays an essential role in metabolism and inflammatory. However, the role of FABP4 in alcoholic steatohepatitis (ASH) remains unclear. This study aimed to investigate the function of FABP4 and the underlying mechanisms in the progression of ASH. Alcoholic hepatitis (AH) datasets were obtained from NCBI Gene Expression Omnibus (GEO). Bioinformatics analysis was performed to screen key genes in FABPs family. Wild-type (WT) and FABP4-deficient (FABP4−/−) mice were subjected to ASH models and the role of FABP4 was investigated. Transcriptional profiling of mouse liver tissue was performed and analyzed by integrative bioinformatics. The Fabp4 associated signaling pathway was further verified. FABP4 was up-regulated in two AH datasets and identified as a critical biomarker. Compared to control, FABP4 is higher expressed in liver tissues of ALD patients and ASH mice. FABP4 deficiency reduced hepatic lipid deposition and inflammation in ASH mice. Mechanistically, FABP4 was involved in regulating the p53 signaling pathway and Sirt1 signaling pathway, subsequently affecting the lipid metabolism and the polarization of macrophages in the liver of ASH mice. FABP4 is involved in the progression of ASH. FABP4 deficiency ameliorates mouse ASH, suggesting that FABP4 may be a potential therapeutic target for ASH.