Researchers at UC Davis have illuminated an important distinction between mice and humans, how human livers heal. The difference centres on a protein called PPARα, which activates liver regeneration. Normally, mouse PPARα is far more active and efficient than the human form, allowing mice to quickly regenerate damaged livers. However, the research shows that protein fibroblast growth factor 21 (FGF21) can boost the regenerative effects of human PPARα. The findings suggest that the molecule could offer significant therapeutic benefits for patients who have had a liver transplant or suffer from liver disease. The opensource study is published in the journal Oncotarget.
The team found that FGF21 is a good rescuing molecule that facilitates liver regeneration and perhaps tissue repair. The data suggests that FGF21 could help with liver regeneration, either after removal or after damage caused by alcohol or a virus.
In the current study, human and mouse PPARα showed different capacities for liver regeneration after surgery. Even after having two-thirds of their livers removed, normal mice regained their original liver mass within seven to 10 days. By contrast, mice with human PPARα never fully regenerated, even after three months. However, by increasing FGF21, the team boosted human PPARα’s ability to regenerate and heal mouse livers.
The team state that while mouse PPARα has regenerative advantages over the human version, there is also a downside, as this ability can lead to cancer. Human PPARα does not cause cancer; however, it cannot match the mouse protein’s regenerative capacity. This trade-off provides a number of advantages on the human side. For example, several popular drugs target PPARα to treat high cholesterol and triglycerides. In the right context, a more active human PPARα could be a great boon for patients with liver conditions. Using FGF21 to boost this regenerative capacity is an important step in that direction.
The current study also adds another line to FGF21’s impressive resume. In addition to boosting human PPARα’s regenerative impact on the liver, the protein has been shown to alleviate insulin resistance, accelerate fat metabolism, and reduce fatty liver disease in animal models.
The researchers explain that FGF21 is a key molecule to regulate metabolism in the liver adding that previous studies show that mice that overexpress FGF21 live 50 percent longer. The data finding show that FGF21 can rescue human PPAR, allowing FGF21 to completely regenerate damaged livers in mice. This could provide significant therapeutic benefits for people after transplants or other liver injury.
Source: UC Davis Health System