Lonidamine ameliorates MASH by reducing SREBP1 and inhibiting the MAPK pathway

• Lonidamine attenuates high-fat, high-cholesterol diet-induced obesity, hyperglycemia, dyslipidemia, inflammation, and hepatic steatosis in a mouse model of MASH. • LND inhibits the MAPK signaling pathway, contributing to its anti-inflammatory effects in MASH. • LND directly interacts with SREBP1 and promotes its degradation, thereby improving abnormal lipid metabolism. • LND represents a promising therapeutic agent for MASH by targeting both inflammation and lipid metabolism.