Research article on pharmacological evaluation using a MASH mouse model has been published in Scientific Reports

2025.11.21

Differences between Therapeutic Mechanisms of Resmetirom and Semaglutide against MASH in Western Diet-Fed MC4R-Knockout Mice

Publication
Published Date : November 20, 2025

In 2024, the first therapeutic drug for MASH, resmetirom (THR-β agonist), was approved by the FDA. In 2025, semaglutide (GLP-1 analog), originally developed as an anti-diabetic and obesity drug, was also approved by the FDA as a treatment for MASH.
In this study, we compared the therapeutic efficacy of Resmetirom and Semaglutide using western diet (WD)-fed MC4R knockout (KO) mice, a MASH model owned by Axcelead. These mice exhibit obesity and insulin resistance, which are clinical features of MASH, and have been reported as a translationally relevant animal model. Both agents significantly improved liver injury markers and hepatic steatosis, consistent with clinical findings, thereby demonstrating the high translational relevance of this model. Semaglutide reduced body weight via appetite suppression and reduction in lean mass, including skeletal muscle. In contrast, Resmetirom maintained lean mass and increased energy expenditure. These results suggest that the two drugs improve MASH pathology via distinct pharmacological mechanisms.

Axcelead DDP Solution
At Axcelead, we offer a wide range of animal models and evaluation indices in the field of metabolic diseases, including WD-fed MC4R knockout mice. Using platforms such as EchoMRI and the Oxymax system, we provide non-invasive assessments of body composition, energy expenditure, and respiratory quotient. In addition, we offer a one-stop service ranging from pharmacological efficacy studies to pathological evaluation. If you are facing challenges in drug discovery for MASH or other metabolic diseases, please feel free to contact us.