Deciphering the hepatic microenvironment: metabolic shifts and intercellular communication in liver steatosis and fibrosis
Deciphering the hepatic microenvironment: metabolic shifts and intercellular communication in liver steatosis and fibrosis
Fatty liver disease, closely linked to overweight and diabetes, is now the most common liver condition worldwide and affects roughly one in three adults. It often begins as a harmless build-up of fat, but in some people it progresses to inflammation and scarring, called fibrosis, which can ultimately cause liver failure or cancer. Effective treatments that halt or reverse this scarring remain very limited. This thesis of Jia Li examines how the different liver cell types drive the disease as it develops, from early fat-related injury to advanced scarring.
A healthy liver depends on several cell types working together. During long-lasting injury, these cells change their behavior and begin to fuel disease. This research approached the problem from two angles, namely how individual liver cells rewire their internal chemistry under stress and how liver cells communicate by exchanging tiny membrane packages that carry molecular messages.
At an early stage, the findings show that a naturally protective protein can shield liver cells from fat-related damage. Later, a drug already used against fibrosis can be repurposed so that, combined with a second agent, it removes the cells that produce scar tissue. The work also shows that some exchanges between liver cells worsen the disease, while others help resolve it, for example by driving scar-producing cells into a permanently inactive state.
Together, these results identify several promising targets for interrupting liver scarring and support combined treatments aimed at the whole cellular network of the diseased liver rather than at one cell type alone.