Resmetirom ameliorates fibrogenesis in hepatic stellate cells via thyroid hormone receptor alpha-fatty-acid amide hydrolase 1 signaling pathway

While Resmetirom hepatocyte-specific effects are well-established, its impact on other hepatic cells, particularly hepatic stellate cells (HSCs), the main fibrogenic cells, remain unknown. Using animal models, immortalized cell lines, and primary murine and human HSCs, we combined pharmacological treatments with genetic manipulation of THRα and fatty acid amide hydrolase (FAAH) to examine the effects of Resmetirom.

Resmetirom ameliorates MASH through actions in both hepatocytes and HSCs. The overexpression of solute carrier organic anion transporter family member 1B1(SLCO1β1) in both cell types increases the efficiency of Resmetirom. THRα expression is higher in HSCs than in hepatocytes in both human and murine cells.