Cellular response mechanisms during lipotoxicity in metabolic dysfunction-associated steatotic liver disease: identification of novel therapeutic targets

Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), commonly known as fatty liver (steatosis), is a significant cause of chronic liver disease worldwide. MASLD is correlated with obesity, diabetes, and cardiovascular diseases and is caused by a lifestyle characterized by diets high in fat, carbohydrates, and calories, along with reduced physical activity. Approximately 25% of the global population is affected by obesity, and a significant portion of these individuals eventually develop MASLD. A primary cause of liver damage in MASLD is lipotoxicity: the damage that occurs to the liver due to exposure to high concentrations of (toxic) free fatty acids, particularly saturated fatty acids like palmitate. This thesis describes research into the mechanisms of lipotoxicity and potential new therapeutic interventions to counteract it.

In summary, this thesis provides new insights into the mechanisms of lipotoxicity, particularly regarding the role of lipid droplets in hepatocytes, and describes several new avenues for the treatment of lipotoxicity, notably involving coffee products.