Professor Lili Liu and Associate Researcher Xuejing Zou's Team: Targeting Macrophages May Offer New Treatment Strategies for IInhibiting MASH Progres

The AASLD 2023 Annual Meeting, hosted by the American Association for the Study of Liver Diseases, recently concluded in Boston, USA. A team led by Professor Lili Liu and Associate Researcher Xuejing Zou from Southern Medical University’s Nanfang Hospital in China, including Physician Ziyong Zhang, presented their research in the field of Metabolism-Associated Steatohepatitis (MASH) during the conference’s oral presentations (Oral 38). Their study suggests that targeting macrophages may offer a new strategy to inhibit the progression of MASH to liver fibrosis. Dr. Ziyong Zhang was invited to introduce their research at the conference and share his experiences and insights.

The study, titled “Hepatocyte-Specific Hif-1α Deletion Accelerates Nonalcoholic Steatohepatitis Progression to Liver Fibrosis,” with Dr. Ziyong Zhang as the first author and Prof. Lili Liu and Xuejing Zou as the corresponding authors, explores the role of hypoxia-inducible factor 1α (HIF-1α) in the progression of MASH, a common chronic liver disease with no effective treatment to inhibit its fibrotic progression.

In their method, the team used the Cre-Lox system to create a mouse model with hepatocyte-specific deletion of HIF-1α and induced MASH using methionine-choline deficient (MCD) or Gubra-Amylin MASH (GAN) diets. They monitored general conditions like food intake and weight changes, as well as biochemical indicators in the serum, liver weight, triglycerides (TC) and total cholesterol (TG) levels, and conducted various analyses to assess hepatic steatosis and fibrosis.

The results showed that, under a normal diet, there was no significant difference between the wild-type mice and those with hepatocyte-specific HIF-1α deletion in terms of physiological changes like weight and serological indicators. However, in the MASH model induced by MCD and GAN diets, the hepatocyte-specific HIF-1α deletion mice showed more severe hepatic steatosis and higher levels of fibrosis. The study also found increased macrophage recruitment in the liver of these mice, with elevated markers like GPNMB and TREM2 in macrophages. In vitro experiments indicated that human recombinant GPNMB protein could promote the activation of hepatic stellate cells, suggesting that hepatocyte-specific HIF-1α deletion might promote MASH progression to liver fibrosis by recruiting macrophages and increasing their secretion of GPNMB protein.

In conclusion, the study found that hepatocyte-specific HIF-1α deletion promotes the progression of MASH to fibrosis in mice by recruiting macrophages, indicating that targeting macrophages might provide a new therapeutic strategy for inhibiting the progression of MASH to liver fibrosis.