Biotechs have yet to discover a therapeutic key for the frustrating disease lock that is nonalcoholic steatohepatitis (NASH). Now, scientists from the University of Michigan have identified a hormone of interest that could pick the lock for worse liver diseases that NASH is a harbinger for. 

The findings, published Monday in Cell Metabolism, center on a hormone primarily secreted by fat cells that had been found to be a checkpoint for further progression of liver disease. A team led by Jiandie Lin had previously uncovered that NRG4 was a critical signifier for liver disease progression in mice with NASH and that increased levels could protect against NASH. Now, the same team has furthered that research, finding that when NASH is already present, a lack of the hormone was linked with a worse case of the disease and more liver tumors. 

"A lot of studies on liver cancer focus on the cancerous liver cells themselves: how they proliferate and how they evade the immune system," Lin said in a press release. "But our findings break out of this liver-centered framework, showing a fat-derived hormone could actually reprogram the liver environment and have a very big impact on liver cancer development."

To validate the impact of the hormone, the team created a NASH mouse model with the gene knocked out in some of the mice. In those cases, there were “significantly increased tumor incidents” and the tumor count was 2.6 times higher compared to the control group without the gene knockout. The scientists also found that without NRG4, there’s a likely exacerbation of the “pathological reprogramming of T-cell transcriptome under metabolic stress conditions.” Furthermore, the T cells that did respond to the environment were more exhausted than in the control group. 

Ref：https://www.fiercebiotech.com/biotech/scientists-hone-hormone-linked-development-liver-cancer-nash-cases