A high-fat diet induces oxidative stress and cytokine storm, leading to the downregulation of melatonin receptor 1A in cardiovascular tissues of rats

Obesity significantly increases the risk of heart disease, making it essential to understand the effects of a high-fat diet (HFD) on cardiovascular health. The overwhelming evidence indicates that high-fat intake may lead to elevated reactive oxygen species levels and mitochondrial damage, both of which impair heart function. This study aimed to investigate the effects of HFD on oxidative stress, inflammation, and melatonin receptor 1A (MT1A) expression in cardiovascular tissues of rats. An experimental rat model was used to assess biochemical, histopathological, and immunohistochemical changes following 12 weeks of HFD exposure. The study analyzed cardiac oxidative stress parameters, pro-inflammatory cytokines in myocardial tissues, serum CRP levels, and evaluated MT1A gene expression in both heart and aortic tissues. HFD markedly increased oxidative stress, as evidenced by significant elevations in MDA and TOS levels, accompanied by substantial reductions in GSH, TAS, SOD and CAT activities (p < 0.001). In parallel, inflammatory responses were significantly enhanced, with increased levels of TNF-α, IL-1β, IL-6 and serum CRP (p < 0.001). Additionally, MT1A expression was downregulated in both myocardial and aortic tissues. This study demonstrates that HFD-induced cardiovascular damage is primarily driven by oxidative stress and inflammation and is accompanied by suppression of melatonin signalling via MT1A downregulation.