Liver knockout YAP gene improved insulin resistance-induced hepatic fibrosis

Yes-associated protein (YAP), as a co-activator of transcription factors, is a downstream protein in the Hippo signaling pathway with important functions in cell proliferation, apoptosis, invasion and migration. YAP also plays a key role in the development of CCl4-induced liver fibrosis. However, the mechanism of YAP during hepatic fibrosis progression and reversion is still unclear. Mild liver fibrosis was developed after 4 months of high-fat diet (HFD) stimulation, and we found that the YAP signaling pathway was activated. Here, we aim to reveal whether specific knockout of Yap gene in the liver can improve liver fibrosis induced by insulin resistance (IR) stimulated by HFD, and further explain its specific mechanism. We found that liver-specific Yap gene knockout improved IR-induced liver fibrosis and liver dysfunction, and this mechanism is related to the inhibition of the insulin signal pathway at the FoxO1 level. These findings provide a new insight, and Yap is expected to be a new target to reverse the early stage of liver fibrosis induced by IR.

Automated summary

Yes-associated protein (YAP) is a downstream protein in the Hippo signaling pathway with key functions in liver fibrosis. Specific knockout of the Yap gene in the liver improves insulin resistance-induced liver fibrosis by inhibiting the insulin signal pathway at the level of FoxO1. This suggests that YAP could be a new target for reversing early-stage liver fibrosis induced by insulin resistance.