PRECISION MEDICINE TO TREAT FATTY LIVER DISEASE

Fatty liver disease (FLD) is a growing burden with hundreds of millions of people affected worldwide. FLD starts with liver fat accumulation and progresses to inflammation, fibrosis and ultimately cirrhosis and cancer. The final stages are life-threatening and are only effectively treated by liver transplantation.

Despite all the efforts, an effective drug treatment against FLD is lacking and remains a major unmet clinical need.Both genetic and environmental factors contribute to FLD onset and progression.

Among the genetic factors, we and others have identified two variants that protect against FLD (in PSD3 and MARC1), but the molecular mechanisms behind their protective effects are unknown.Among the environmental determinants, obesity is without any doubt the major risk factor for FLD. However, some obese individuals seem to be protected against the disease.

The mechanisms underlying the protection against FLD in these at-risk individuals remain unknown.Our aim is to understand the protection against FLD.

This will be achieved firstly by elucidating the molecular genetics underlying the PSD3 and MARC1-related protection against FLD.

Then by identifying novel genetic variants, metabolic pathways and lipidomic fingerprint responsible for FLD protection in individuals with morbid obesity.Understanding the mechanisms behind FLD protection will lead to the identification of effective and tailored drug treatments to treat this condition in the framework of precision medicine.