Metabolic-associated fatty liver disease (MASLD), a condition impacting roughly 30% of individuals globally, has long lacked effective and targeted therapeutic options. However, recent groundbreaking research has pinpointed a crucial genetic factor that exacerbates this condition. Even more surprisingly, the most effective strategy to target this factor appears to be a widely available and already approved treatment: vitamin B3 (niacin).
MicroRNA-93 Identified as a Central Regulator
An international research collaboration, led by Professor Jang Hyun Choi at UNIST, in conjunction with Professor Hwayoung Yun at Pusan National University and Professor Neung Hwa Park at Ulsan University Hospital, has pinpointed microRNA-93 (miR-93) as a pivotal regulator in MASLD. This discovery marks the first time this specific molecule has been clearly linked to the development and progression of the disease.
How miR-93 Disrupts Liver Function
MiR-93 is a tiny RNA molecule found within liver cells that controls the activity of certain genes. Researchers observed unusually high levels of miR-93 in both human patients with fatty liver disease and in animal models. Their analysis revealed that elevated miR-93 promotes fat accumulation, inflammation, and scarring in the liver by suppressing SIRT1, a vital gene involved in managing fat metabolism inside liver cells.
To further understand its functional role, the team utilized gene editing techniques to halt miR-93 production in mice. These genetically modified animals exhibited significantly less fat accumulation in the liver, alongside improved insulin sensitivity and enhanced overall liver function. Conversely, mice engineered to produce excessive amounts of miR-93 developed more severe metabolic issues within their livers.
Vitamin B3 Shows Promise as a Therapeutic Agent
Following these insights, the researchers screened 150 FDA-approved drugs to identify any that could reduce miR-93 levels. Niacin, also known as vitamin B3, emerged as the most effective candidate. In mice treated with niacin, miR-93 levels sharply declined, while SIRT1 activity increased. This favorable shift helped to restore normal fat-processing pathways in the liver and improved the overall balance of lipids.
The research team emphasized, “This study precisely elucidates the molecular origin of MASLD and demonstrates the potential for repurposing an already approved vitamin compound to modulate this pathway, which has high translational clinical relevance.” They further added, “Given that niacin is a well-established and safe medication used to treat hyperlipidemia, it holds promise as a candidate for combination therapies targeting miRNA pathways in MASLD.”