Resmetriom-treatment reduces expression of fibrosis-associated genes in hepatic stellate cells

The global prevalence of metabolic-associated steatotic liver disease (MASLD) is around 25%, and a further increase is expected in the future. MASLD and metabolic syndrome constitute significant health threats worldwide, due to their strong association with increased morbidity, mortality, and their status as leading causes of chronic liver disease. Previous research has identified the role of the thyroid hormone signaling pathway as a potential therapeutic approach, particularly the function of the thyroid hormone receptor beta (TRβ). Resmetirom is the first drug approved by the EMA for the treatment of adults with MASH fibrosis (F2-F3). As a partial agonist of the TRβ resmetirom acts selectively on the TRβ, which plays a key role in regulating fat metabolism in the liver. The objective of this project is to investigate the effects of the TRβ analogue resmetirom on LX2 cells and primary human hepatic stellate cells (phHSC) in a cell culture model. The cells were incubated for 24 and 48 hours with different concentrations of resmetirom and with or without TGF-beta, followed by gene expression analysis using quantitative real-time PCR for fibrosis-associated genes such as aSMA and Col1a1. Treatment of the cells with TGF beta alone caused an increase of the expression of the pro-fibrotic genes aSMA and Col1a1 in LX2 and phHSC. In combination with resmetirom, the expression of pro-fibrotic genes was not as high as with TGF beta alone. The findings indicate that resmetirom exerts a direct anti-fibrotic effect through modulation of hepatic stellate cell activity. Publication History Article published online: 26 January 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany