Exploring the therapeutic potential of mitochondrial mechanism in metabolic dysfunction associated steatotic liver disease

Abstract

Metabolic dysfunction-associated steatotic liver disease has emerged as the most prevalent liver disease with a rapidly increasing incidence worldwide. Targeting mitochondria in this condition opens up innovative avenues for the development of new therapeutic molecules. Mitochondrial dysfunction potentially influences the pathways of this disease and facilitates lipid accumulation and inflammation in hepatocytes, which can be targeted and reversed in the liver. Mitochondria are crucial in signalling pathways that regulates oxidative stress and fatty acid are essential for maintaining the integrity of hepatocyte. Mitochondrial dysfunction significantly influences the onset and progression of metabolic dysfunction-associated steatotic liver disease, revitalising the research of steatotic liver therapy. The limited availability of treatment strategies arises from the heterogeneity of the disease pathology, and for a considerable time, insights into the aetiology of the disease remained unclear. Until very recently, treatment options for managing the condition were limited to antidiabetic, anti-inflammatory, and miscellaneous drugs. However, Resmetirom has emerged as the only FDA-approved drug, that specifically targets the thyroid hormone receptor-β receptor in the liver. More direct and targeted therapies are essential for this condition. Targeting the mitochondrial dysfunction significantly expands the landscape of therapeutic potential, facilitating the introduction of additional therapies aimed at preventing, managing, or curing the condition, alongside the traditional therapies currently available.