A research team from the Hefei Institutes of Physical Science (HFIPS) of the Chinese Academy of Sciences has reported their discovery that a metabolic regulation mechanism may play a role in transformation of non-alcoholic steatohepatitis into malignant liver tumors.

The study team led by Yang Wulin spent more than two years on this work that was published in the International Journal of Biological Sciences.

Fatty liver, just as its name suggests, is a common disease marked by an excessive accumulation of fat in liver cells.

Model diagram: In the NASH stage, a variety of oncogenic signals and the fatty acid metabolism signal axis are activated in concert, which is conducive to the formation of tumor stem cells and malignant transformation. [IMAGE: LIU YU]

There are two categories of fatty liver disease; non-alcoholic fatty liver disease (NAFLD) is the one the team explored. Gradually becoming the main type of fatty liver disease, the non-alcoholic variety may progress stage by stage, eventually reaching the key stage of non-alcoholic steatohepatitis, usually called NASH, which may then turn into liver cancer.

The team was curious about that last development. They planned to conduct a study to reveal the mechanism of how non-alcoholic steatohepatitis progresses to liver cancer.

Their work began with a mouse model that mimics the development of human fatty liver disease and enables study of changes in gene expression information that occur at various stages in the progression of NAFLD.

In each stage of the disease, they conducted deeper analysis on gene differential expressions and gene set variations, finding that carcinogenic signals were extensively activated during NASH. They also found that fatty acid metabolism was specifically regulated and increased by the LPL/FABP4/CPT1 signal axis. The two may work together to promote tumor-initiating cell formation and begin malignant transformation.

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

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

The team believes that inhibition of the fatty acid metabolic signaling axis may prevent NAFLD from transforming into liver cancer, shedding new light on prevention of NASH-related liver cancer.

For more information, please contact:

Dr. & Professor Yang Wulin

E-mail: yangw@cmpt.ac.cn

Institute of Health and Medical Technology,

Hefei Institutes of Physical Science (HFIPS),

Chinese Academy of Sciences

Source: Institute of Health and Medical Technology,

Hefei Institutes of Physical Science (HFIPS),

Chinese Academy of Sciences