Semaglutide reduces cardiomyocyte damage caused by high-fat through HSDL2

Background The expression of inflammation and oxidative stress caused by obesity is high, which has a certain degree of damage to myocardial cells. is a glucagon-like peptide-1 receptor agonist, which has a hypoglycemic and weight loss effect. Similarly, hydroxysteroid dehydrogenase-like protein 2 (HSDL2) can also regulate lipid metabolism. However, it is not clear whether smegroupide reduces obesity-related cardiomyocyte damage through HSDL2. In this study, the oxidative stress index of the serum of mouse cardiomyocytes and obese mice in a high-fat environment and the expression of HSDL2 were detected to reveal the mechanism of obesity-induced cardiomyocyte injury and the effect of semaglutide in reducing cardiomyocyte injury regulated by HSDL2. Methods In this study, animal models of mice in the obesity group and the micetigrupide intervention group, the cardiomyocyte model of palmitic acid cultured mice in ordinary and knockout HSDL2, and the cell model of the miceglupeptide intervention were established. The levels of inflammatory and oxidative stress indicators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen (ROS) and malondialdehyde (MDA) in mouse serum and mouse cardiomyocytes were also detected. Then, the expression of HSDL2 of normal mouse cardiomyocytes cultured with high fat culture and mouse cardiomyocytes that knocked HSDL2, as well as the oxidative stress and autophagy levels of cells, were measured, and the effect of semaglutide regulation by HSDL2 on cardiomyocyte damage caused by high fat was evaluated. Conclusion Obesity increased the oxidative stress level of mouse cardiomyocytes and mouse serum, while semaglutide can reduce the increased oxidative stress level caused by obesity. At the same time, semaglutide also significantly reduced the weight of obese mice. The myocardial tissue and myocardial cells of mice in the obese group showed an upward expression of HSDL2, but after the intervention of semaglutide. After knocking out HSDL2, the level of ROS and autophagy of mouse cardiomyocytes decreased significantly. Semaglutide may reduce cardiomyocyte damage caused by high fat by regulating the expression of HSDL2. These findings are expected to reveal the new molecular mechanism of semaglutide to regulate obesity-related cardiomyocyte injury through HSDL2, providing a new target for clinical treatment.