Metabolic-associated fatty liver disease:a major problem miniaturised

Fatty liver disease (known as MAFLD or NAFLD), mirroring the prevalence of obesity, is a condition on the rise. Obesity and the consumption of a so-called Western diet expose the liver to high levels of sugar, fat and insulin. These circumstances instigate hepatic fat accumulation. The accumulation of fat predisposes the liver to inflammation, scarring, cirrhosis and even cancer. There is no treatment for MAFLD or advanced stages of this disease.The thousands of studies aimed at understanding and treating MAFLD have not led to a clinically approved therapy so far. A possible hindrance in such research efforts is the lack of appropriate study models. Unfortunately, preclinical research relies mainly on animal testing and cell cultures, neither of which is ideal. This thesis describes a method to use human liver tissue that was considered surgical waste for research of MAFLD. By preparing precision-cut liver slices (PCLSs) and exposing these to nutrients, the most harmful nutrients were identified. Exposure to a Western diet pushed PCLSs towards a MAFLD phenotype that included drastic increases in fat accumulation and inflammation within 24 hours, which made the model suitable to test potential interventions. Reflecting the findings of clinical trials, the investigated therapies yielded mixed results in PCLSs. Still, some compounds successfully increased fat catabolism and reduced fat accumulation. This further validated the model, which could prove valuable for future MAFLD research. The fatty liver slices bring us one step closer to treatment of MAFLD, meanwhile providing a great alternative to animal testing