Effects of Semaglutide on Cardiac Protein Expression and Cardiac Function of Obese Mice

Abstract

Using proteomics to study the effect of semaglutide on cardiac protein expression in obese mice. Assessment of the effect of semaglutide on cardiac function in obese mice. Materials and Methods:The mice were randomly divided into three groups: the control group (WC), the high-fat group (WF), and the high-fat diet with semaglutide intervention group (WS). Serum samples were collected, and lipids, blood glucose, inflammatory and oxidative stress markers, and cardiac ultrasound, were examined. The cardiac weight of each group of mice was measured, and pathological alterations were examined. Inflammation and oxidative stress levels in heart tissue were evaluated. The labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was used to find differentially expressed proteins (DEPs) and screen for related pathways and key proteins in a proteomics study. Results: Semaglutide greatly alleviated obesity-induced lipid metabolism abnormalities, improved cardiac ventricular wall thickening, and significantly reduced myocardial collagen content in obese mice. Semaglutide significantly reduces obesity-induced inflammation and oxidative stress. There were 64 DEPs in the WF/WC group, with 39 upregulated proteins and 25 downregulated proteins. The WS/ WC group, on the other hand, had 83 DEPs, including 57 upregulated and 26 downregulated proteins. Following functional analysis, DEPs were shown to be largely associated with lipid metabolism and peroxisomes. Apolipoprotein A-II, catalase, diazepam-binding inhibitor, paraoxonase-1, and hydroxysteroid 17-dehydrogenase-4 were all upregulated in the WF group but significantly downregulated in the WS group. A high-fat diet increases the expression of lipid synthesis and transport proteins while increasing inflammation and oxidative stress damage. Conclusion: Semaglutide decreases lipid synthesis alleviates inflammation and oxidative stress and prevents lipid peroxidation and cardiac impairment.

Epidemiological Characterisation of Chronic Diseases Among Civil Servants in Hebei Province, China: A Cross-Sectional Real-World Study of Approximately 50,000 Adults

“…Obesity is now widely recognised as a risk factor for various chronic ailments and is closely linked with an elevated occurrence of diabetes, hypertension, and cardiovascular and cerebrovascular diseases. 11 , 12 Available data suggest that in 2018, the proportion of individuals suffering from obesity in China had risen by more than two-fold to 8.1% from 3.1% in 2004. 13 A recent study found that 15.8 million Chinese adults have a current prevalence of obesity of 14.1% and overweight of 34.8%.…”

Anti-inflammatory benefits of semaglutide: State of the art

“… Effects Model Treatment Ref. Reduced the TNF-α, IL-6 and Nf-κB signalings LPS-induced lung injury in rats Semaglutide [73] Blocked the NLRP3 activity PTT-induced seizure in C57/BL6J mouse Semaglutide [70] Reduced the TNF-α, IL-6, and IL-1β levels in brain tissues Endo-toxemia in male Swiss albino mice Semaglutide [72] Reduced p38 MAPK, c-Jun- NF-κB p65 inflammation signaling pathway in brain tissues Animal model of seizure Semaglutide [71] Reduced intramuscular fat and improved muscle function by lowering the, TNF-α, IL-6, IL-1β levels Male C57BL/6 mice Semaglutide [78] Declined TNF-α, and IL-6 serum and heart tissues Obese mouse Semaglutide [62] Decreased vascular inflammation and micro-calcifications Obese rabbit Semaglutide [79] Attenuated inflammatory markers and improved cardiac function Obese mice Semaglutide [80] …”

“…Additionally, they are associated with pathological conditions such as obesity, which is characterized by underlying chronic inflammation [62] . There is evidence suggesting that semaglutide indirectly exerts anti-inflammatory effects by suppressing these mediating mechanisms [19] , [62] , [80] . It has been shown to reduce oxidative stress-dependent inflammation in H9c2 cells treated with LPS through an AMPK-dependent pathway, leading to decreased production of reactive oxygen species (ROS) and lower levels of NF-κB, TNF-α, and IL-1β [19] .…”

“…It has been shown to reduce oxidative stress-dependent inflammation in H9c2 cells treated with LPS through an AMPK-dependent pathway, leading to decreased production of reactive oxygen species (ROS) and lower levels of NF-κB, TNF-α, and IL-1β [19] . Furthermore, semaglutide has been found to ameliorate obesity-induced inflammation by down-regulating S100a8, S100a9, and Cxcl2 in neutrophils of obese mice [62] , [80] . It has also demonstrated a reduction in obesity-dependent inflammation in obese mice [91] .…”

Effects of High-Fat Diet on Cardiovascular Protein Expression in Mice Based on Proteomics

“…In addition, obesity can increase the risk of cardiovascular disease, affect the function of the endocrine system and increase the risk of cancer. 3–5 Therefore, obesity is a disease syndrome that deserves our continuous attention.…”