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Cellular and molecular mechanisms of Resmetirom in metabolic dysfunction-associated steatohepatitis (MASH): A transcriptomic profiling study

GSE310831 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/11/21 Platform GPL34290
Summary
This study demonstrates that the thyroid hormone receptor-β (THR-β) agonist Resmetirom, the first FDA-approved anti-MASH drug, exerts potent therapeutic effects in a human relevant dietary mouse model of metabolic dysfunction–associated steatohepatitis (MASH) induced by fructose, palmitate, and cholesterol (FPC). Resmetirom treatment markedly improved hepatic steatosis, inflammation, and fibrosis, accompanied by reduced systemic inflammatory markers and hepatocyte death. Transcriptomic profiling revealed that Resmetirom profoundly reprograms hepatic gene expression, particularly suppressing pathways involved in lipid metabolism, inflammation, and multiple forms of programmed cell death, including apoptosis, pyroptosis, and necroptosis. These findings highlight a previously unrecognized role of THR-β activation in regulating hepatocyte survival and inflammation, providing mechanistic insight into the multifaceted hepatoprotective effects of Resmetirom in MASH.
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Direct links to NCBI, no account and no request form: the whole study as GSE310831_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1367129 and SRA study SRP647344. Searching any of these in the dataset finder brings you back here.

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