Hepatic miR-93 promotes the pathogenesis of metabolic dysfunction-associated steatotic liver disease by suppressing SIRT1

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a global health challenge with limited therapeutic options, and its molecular mechanisms remain poorly understood. Here, we identify microRNA-93 (miR-93) as a critical regulator of MASLD progression. miR-93 was markedly upregulated in liver tissues from both MASLD patients and diet-induced obese mice. miR-93 knockout (KO) mice were protected against diet-induced hepatic steatosis and fibrosis, along with improved glucose tolerance and enhanced mitochondrial function. Transcriptomic analysis revealed that miR-93 directly targets Sirtuin 1 (SIRT1), suppressing the LKB1-AMPK signaling pathway, which disrupts lipid metabolism. Notably, pharmacological inhibition of miR-93 using niacin restored SIRT1 activity, alleviating MASLD symptoms and improving metabolic function. Our findings establish miR-93 as a novel and promising therapeutic target in MASLD. The modulation of the miR-93/SIRT1 axis, particularly through niacin treatment, presents a potential therapeutic avenue for MASLD, a disease with few current treatment options.