Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disorder that develops alongside risk factors such as obesity and type 2 diabetes (T2DM). Current pharmacological approaches are insufficient for the treatment. Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, is used to treat T2DM and obesity. It enhances insulin secretion and reduces appetite. Recent studies indicate that semaglutide mediates significant improvements in MASLD. Purpose The aim of this study was to generate a rat model of MASLD and then investigate the acute effect of semaglutide on rat aortas. Method Male Wistar rats were fed a high-fat diet (HFD) for either six or eight weeks in order to induce MASLD. Blood glucose levels were evaluated using an oral glucose tolerance test. A histological evaluation was conducted on the livers. Biochemical parameters were evaluated in blood samples taken at the time of sacrification. Aortic responses to KCl, phenylephrine, acetylcholine, and semaglutide were assessed in isolated organ bath. The effect of semaglutide was also examined in the presence of various inhibitors. Results Blood glucose, total cholesterol and triglyceride levels were significantly higher in MASLD rats than in the control group. Histopathological evaluations of liver tissues indicated that 8-week HFD administration shaped steatohepatitis as a result of mononuclear cellular infiltration, degeneration, and the presence of hyperemia. Vascular responses to both phenylephrine and acetylcholine were lower in MASLD rats. Interestingly, semaglutide induced a strong vasodilation, particularly in the control group. This vasodilation was reversed by a K+ channel inhibitor. Conclusion Exposure to a high-fat diet (HFD) for eight weeks produces a better MASLD model. This is an important finding for our future investigations where we plan to slow the progression of the disease with drugs. Semaglutide may also be considered for cardiovascular effects in this model in addition to its known effects related to metabolism which in our opinion may be connected through K+ channels.
Ciloglu et al. (Fri,) studied this question.