Revolutionary Breakthroughs

Traditional treatment strategies for metabolic dysfunction steatotic liver disease (MASLD), focused primarily on lifestyle modification to ameliorate obesity and insulin resistance, are often inadequate, especially in advanced stages or in patients who do not respond to lifestyle changes. This has led to a significant shift towards the identification of new therapeutic targets through various biological pathways crucial to the pathogenesis of the disease. In this chapter we discuss advances in the treatment of hepatic lipid metabolism as a therapeutic strategy for MASLD, including the promising roles of specific enzyme inhibitors such as acetyl-CoA carboxylase (ACC), diacylglycerol acyltransferase 2 (DGAT2), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1). In addition, we delve into the potential of nuclear receptors such as farsenoid X receptor (FXR) and peroxisome proliferator-activated receptors (PPAR) in modulating liver function and mitigating disease progression. Additionally, we address innovative approaches in modulating the gut microbiota, including the use of probiotics, prebiotics, and fecal microbiota transplantation (FMT), to address the gut-liver axis and its involvement in MASLD. Finally, the exploration of gene therapies and personalized medicine presents an exciting frontier to effectively address the genetic underpinnings of MASLD, offering hope for tailored and more effective interventions.