Abstract
Abstract
Introduction: Semaglutide (SEM) is a novel glucagon-like peptide-1 receptor agonist that can efficiently treat type-2 diabetes and obesity. Although it has a very important role in the cardiovascular system, it may be associated with various adverse effects. Aim: to explore the role of adiponectin, TNF-α, and caspase-3 as potential mechanisms that could be related to SEM's impact on the cardiac muscle of both obese and non-obese albino rats. Materials & methods: For this study, 40 adult albino rats (250-280 g) were grouped into: Regular standard diet (RD) as control group; high-fat diet (HFD) group; SEM + RD group; and SEM + HFD group. Results: The HFD group displayed a remarkable increment in body and heart weight, total cholesterol, triglycerides, LDL, cardiac troponin I, serum levels of TNF-α, cross-sectional area of cardiac fibres, mean area percentage of collagen fibres, activated caspase-3, and NF-κB immunostaining. Also, a significant decrement in HDL and adiponectin serum levels, notable histological and electron microscopic alterations. The SEM + HFD group exhibited marked improvements in these biochemical, histological, and electron microscopic findings, except for apparently decreased body & heart weight and cardiac fibres’ cross-sectional area compared to the HFD group. Whereas the SEM + RD group revealed a non-significant difference compared to the control, except for an apparent reduction in body & heart weight and cardiac fibres' cross-sectional area. Conclusion: SEM was found to improve HFD-induced myocardial alterations, yet it reduced cardiac muscle size in obese and non-obese rats. Therefore, it should be used very cautiously for weight reduction, especially for long-term use.