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PurposeThe aim of this study was to evaluate changes in body weight, liver weight, blood glucose, liver injury markers, pro-inflammatory factors and oxidative stress marker levels in obese mice with HFD induced NAFLD after semaglutide use.Patients and methodsThe 24 C57BL6J mice were randomly divided into three groups (NCD, HFD and Sema) for the assessment of metabolic status, inflammatory factor and oxidative stress marker levels, liver histopathology in mice. Liver metabolomics was determined by liquid chromatography/mass spectrometry (LC-MS) method.ResultsThe mice body weight, liver weight, blood glucose, TG, TCHO, LDL and pro-inflammatory factors were significantly reduced after semaglutide. Meanwhile, semaglutide increased the SOD level. Semaglutide treatment significantly improved the pathological changes such as hepatocyte steatosis, balloon degeneration and lymphoid foci by HE. It also significantly reduced lipid droplet by Oil Red O. The mitochondria were swollen, the volume increased, the cristae were partially broken and reduced, the intramembrane matrix was partially dissolved, and the mitophagy structure was visible in the visual field. There were 6 metabolites down-regulated and 2 metabolites significantly up-regulated after semaglutide treatment.ConclusionsSemaglutide can reduce blood glucose level and liver fat accumulation and play an anti-inflammatory role in advanced NAFLD that due to the effects of HFD.

Purpose This study aimed to investigate the effect of Semaglutide on skeletal muscle and its metabolomics. Methods A total of 18 male C57BL/6 mice were randomly divided into normal control (NC) group, high-fat diet (HFD) group and HFD+Semaglutide group, and were given standard diet, HFD diet, HFD diet plus Semaglutide, respectively. The body weight, gastrocnemius weight, serum lipid, blood glucose and inflammatory index levels of mice in each group were observed and compared, and the morphological and structural changes of gastrocnemius were also analyzed. Meanwhile, gastrocnemius metabolite changes were analyzed by untargeted metabolomics. Results After Semaglutide treatment, the food intake and body weight of mice were evidently decreased, while the relative gastrocnemius weight ratio were conversely increased. Meanwhile, the levels of TG, CHO, LDL, HDL, TNF-α, IL-6, IL-1β and HOMA-IR were all observed to decrease remarkably after Semaglutide intervention. Histological analysis showed that Semaglutide significantly improved the pathological changes of gastrocnemius, manifested as increased type I/type II muscle fiber ratio, total muscle fiber area, muscle fiber density, sarcomere length, mitochondrial number and mitochondrial area. Furthermore, metabolic changes of gastrocnemius after Semaglutide intervention were analyzed, and 141 kinds of differential metabolites were screened out, mainly embodied in lipids and organic acids, and enriched in 9 metabolic pathways including a variety of amino acids. Conclusion Semaglutide can significantly reduce the body weight and the accumulation of intramuscular fat, promote muscle protein synthesis, increase the relative proportion of skeletal muscle, and improve muscle function of obese mice, possibly by altering the metabolism of muscle lipids and organic acids.

Using proteomic techniques the impact of the sodium-glucose transport protein 2 inhibitor empagliflozin on cardiac protein expression in a mouse model was assessed under normal and high-fat diet (HFD) conditions. We examined the effect of obesity on serological markers and heart function in obese mice treated with or without empagliflozin and used proteomic techniques to investigate alterations in cardiac protein expression. Using bioinformatic techniques, data were screened for differentially expressed proteins (DEPs) implicated in the putative mechanism of empagliflozin's cardioprotective effects. In C57BL/6 mice, HFD increased body weight, blood lipid, and glucose levels and was associated with structural damage to the heart. Empagliflozin reduces body weight, improves glucose and lipid metabolism, alleviates obesity-induced cardiac ventricular wall thickening, and lowers cardiac tissue collagen. The expression of several proteins was altered in the heart, mainly related to lipid metabolism. Following empagliflozin treatment, the expression of several lipid metabolism-related proteins was considerably reduced. Further examination of DEPs revealed that following empagliflozin treatment, the expressions of Apoe, Apoc1, Saa2, Apoa2, and Pon1 altered dramatically, suggesting that these proteins may be the main proteins that empagliflozin uses to treat obesity-induced aberrant lipid metabolism. Empagliflozin may protect the heart by altering the expression of genes including Apoe, Apoc1, Saa2, Apoa2, and Pon1, which are all involved in lipid metabolism disturbance in obesity.