The pathological role of A-FABP in the development of liver fibrosis

Abstract

Background and objectives: Circulating levels of adipocyte fatty acid binding protein (A-FABP) are closely associated with liver fibrosis and inflammation in patients with nonalcoholic fatty liver disease (NAFLD). However, there are no in vivo studies to explore the role of A-FABP in liver fibrosis. In the present study, A-FABP knockout (KO) mice were generated for the loss of function study and three liver fibrosis mouse models: carbon tetrachloride (CCl4) injection, bile duct ligation (BDL) and high fat high cholesterol (HFHC) diet induced mouse models were employed to investigate the pathological role of A-FABP in liver fibrosis.

Key findings: 1. Morphological analysis of liver and quantitative PCR of the hepatic expression of fibrotic markers showed that liver fibrosis was successfully established on wild-type (WT) mice treated with CCl4 injection or BDL, and wild type and A-FABP knockout (KO) mice fed on HFHC diet. 2. HFHC diet induced liver fibrosis was alleviated in A-FABP KO mice when compared to WT control. 3. Circulating A-FABP was significantly increased in both CCl4 injection and BDL induced mouse models. 4. The mRNA expression of A-FABP was elevated in the liver tissue of BDL-, CCl4- and WT-HFHC diet induced mouse models.

Conclusions: Circulating and hepatic A-FABP increased in CCL4- and BDL-induced liver fibrosis mouse models. A-FABP deficiency protects against HFHC-induced liver fibrosis in mice. These results indicate that A-FABP is associated with the development of liver fibrosis and may be a potential fibrotic biomarker and therapeutic target for anti-fibrotic drug development.