CDA HFD mice analysed for hepatic gene expression after treatment with semaglutide
Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. We show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation, and reduced hepatic expression of fibrosis- and inflammation-related gene pathways. NOTE: dose is 20 µg/kg QD as stated in the publication, not 10 nmol/kg as stated in the fastq file names! Overall design: CDA HFD mice were analysed for hepatic gene expression after treatment with semaglutide. Male C57BL/6JRj mice (7–8 weeks old) were obtained from Taconic (Ejby, Denmark) and housed in a controlled environment (12-h light/dark cycle, lights on at 6 AM, 21 ± 1.0°C, humidity 45–65%). Mice had ad libitum access to tap water and either chow or a high-caloric CDA-HFD diet (kcal %; fat 60%, carbohydrates 20%, 5.2 kcal/g, #A06071302, Research Diets, New Brunswick, NJ, USA) for 6 weeks prior to treatment start. CDA-HFD mice were randomly allocated to groups and treated with vehicle or semaglutide 20 µg/kg  for 6 (called 6-12w) or 12 weeks (called 6-18w). A group of CDA-HFD mice were terminated at treatment start to determine baseline levels of NASH ( baseline group). Vehicle-dosed chow-fed mice and mice switched to chow and does with vehicle served as additional controls.  Vehicle-dosed chow-fed mice and mice switched to chow and dosed with vehicle served as additional controls. Dosing was performed subcutaneously once daily in a volume of 5 ml/kg. To reduce initial gastric discomfort, the dose was increased through daily increments until reaching the target dose on treatment day 5.