Studies reveal how fatty liver disease turns into liver cancer

Model diagram: At the NASH stage, various carcinogenic signals and fatty acid metabolism signal axes are activated in a coordinated manner, promoting the formation of tumor stem cells and the development of malignant transformation. Credit: Liu Yu

Researchers at the Hefei Institute of Materials Science (HFIPS) of the Chinese Academy of Sciences have reported the discovery that metabolic regulatory mechanisms may play a role in malignant transformation from nonalcoholic steatohepatitis to liver tumors.

A research team led by Jan Woolin has spent more than two years publishing this work. International Journal of Biological Sciences last month.

Fatty liver, as its name suggests, is a common disease of the liver characterized by the excessive accumulation of fat in the cells.

There are two categories of fatty liver disease, and the team investigated non-alcoholic fatty liver disease (NAFLD).Gradually ingest non-alcoholic fatty liver disease, which is a major part of fatty liver disease Liver disease It progresses in stages, but non-alcoholic steatohepatitis (usually called NASH) is an important stage because it can lead to liver cancer.

The team was interested in turning. They planned to conduct a study to elucidate the mechanism by which nonalcoholic steatohepatitis progresses to liver cancer.

Their job is Mouse model It imitates human development Fatty liver Disease by studying changes in gene expression information that occur at various stages of NAFLD progression.

At each stage of the disease, they conducted a deeper analysis of differential expression of genes and changes in gene sets. Later, they discovered that carcinogenic signals were extensively activated during NASH. Moreover, Fatty acid metabolism Those tuned by the LPL / FABP4 / CPT1 signal axis were especially upregulated. The two work together to promote the formation of tumor-initiating cells and initiate malignant transformation.

Based on these analyses, the team conducted further laboratory studies and showed that inhibition of the LPL / FABP4 / CPT1 signaling axis effectively inhibited the growth of liver tumors in vivo.

In addition, in vitro cell experiments also confirmed that targeted inhibition of the metabolic axis significantly reduced the self-renewal and proliferative capacity of liver cancer stem cells.

The team believes that inhibition of the fatty acid metabolism signaling axis may prevent the transformation of NAFLD into liver cancer and shed new light on the prevention of NASH-related liver cancer.

Genetic association with newly discovered non-alcoholic inflammatory liver disease

For more information:
Target inhibition of Haoran Yang et al, LPL / FABP4 / CPT1 fatty acid metabolism axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer. International Journal of Biological Sciences (2021). DOI: 10.7150 / ijbs.64714

Provided by Hefei Physics Research Institute, Chinese Academy of Sciences

Quote: The study sheds light on how fatty liver disease turns into liver cancer (November 29, 2021).

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Studies reveal how fatty liver disease turns into liver cancer

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