FAM3B activates hepatic stellate cells to accelerate hepatic fibrosis by promoting glucose metabolism.

This study aimed to investigate the role and mechanism of FAM3B (family with sequence similarity 3 member B) in hepatic fibrosis. Bioinformatics analysis, immunohistochemistry, Masson staining, and immunofluorescence detection revealed that the expression of FAM3B was significantly elevated in human hepatic fibrosis tissues and positively correlated with serum HBV DNA load and collagen deposition. Using lentiviral overexpression of FAM3B in the HSC-T6 cell model and siRNA knockdown experiments, we confirmed that FAM3B overexpression promotes hepatic stellate cell (HSC) activation by enhancing glucose metabolism (indicated by increased glucose uptake, upregulation of key glycolytic enzymes GLUT1, GLUT3, HK2, LDHA, PFKP, and PKM2, elevated extracellular acidification rate, and increased lactate production) and upregulating HK2 promoter transcriptional activity. This leads to increased α-SMA and COL1α1 expression, enhanced cell proliferation, and suppressed apoptosis, effects that were reversed by the glycolysis inhibitor 2-deoxyglucose (2-DG). In vivo, FAM3B overexpression exacerbated CCl4-induced liver fibrosis and collagen deposition in mice, while 2-DG intervention significantly alleviated this process. CONCLUSION: FAM3B accelerates HSC activation and hepatic fibrosis progression by enhancing glucose metabolism.