Carbon tetrachloride does not promote hepatic fibrosis in ob/ob mice via downregulation of lipocalin-2 protein.

Although leptin-deficient ob/ob mice have been investigated to determine whether hepatic steatosis promotes susceptibility to hepatotoxic insults, carbon tetrachloride (CCl)-induced hepatic fibrosis in ob/ob mice remains largely unknown. In this study, we evaluate the pathogenic mechanisms of hepatic fibrosis in CCl-treated wild-type (WT) and ob/ob mice and analyze some parameters related to lipogenesis, inflammation, fibrosis, oxidative stress, apoptosis, and autophagy. CCl treatment attenuated liver weight and lipogenesis in ob/ob mice. Increased hepatic fibrosis-related proteins were reduced in CCl-treated ob/ob mice compared with CCl-treated WT mice. Specifically, the expression of lipocalin-2 (LCN2) was markedly reduced in CCl-treated ob/ob mice versus CCl-treated WT mice. Compared with CCl-treated WT mice, CCl-treated ob/ob mice had reduced expression of neutrophil-related inflammatory genes and proteins. Hepatic heme oxygenase-1 protein was reduced in CCl-treated ob/ob mice compared with CCl-treated WT mice. However, CCl did not promote hepatic apoptosis in ob/ob mice. Therefore, these findings highlight LCN2 as a key signaling factor in CCl-induced hepatic fibrosis.