The Role of Fish Oil in Modulating Metabolic Disorders: Implications for Cardiovascular Health, Endothelial Dysfunction Biomarkers, and Hypercholesterolemia.

Background: Hypercholesterolemia is a significant risk factor for various metabolic disorders, such as diabetes, cardiovascular disease (CVD), and atherosclerosis, which contribute to morbidity and mortality worldwide. Fish intake has been associated with a lower risk of CVD; however, the administration of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) has shown limited effects on cholesterol levels. Aims: This study aimed to investigate the role of fish oil in maintaining a healthy metabolism; explore the impact of hypercholesterolemia on oxidative stress, endothelial dysfunction, and inflammatory biomarkers; and determine the biochemical relationships among lipid profiles, inflammatory mediators, and endothelial dysfunction biomarkers. Additionally, we compared the potential roles and mechanisms of action of fish oil and atorvastatin in the treatment and prevention of cardiovascular events. Methods: Eighty rats, weighing 100-150 g, were divided into five equal groups. The first group (control) was fed a standard diet. The second group was fed a high-cholesterol diet (HCD) for 8 weeks to induce hypercholesterolemia. The third group was given HCD supplemented with fish oil. The fourth group received HCD along with 20 mg of atorvastatin. Blood and tissue samples were analyzed to measure serum lipid profiles, including triglycerides (TG), cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and homocysteine levels. Inflammatory mediators (C-reactive protein, TNF, IL-6) and endothelial dysfunction markers (nitric oxide, nitric oxide synthase) were also measured. The statistical analysis method used for the study was one-way analysis of variance (ANOVA). Results: Compared to the control group, the final body weight and mean body weight gain were significantly greater in the HCD group. The HCD-fed rats exhibited increased levels of serum lipids, including LDL, TG, total cholesterol (TC), and HDL (P < 0.05), as well as elevated heart function markers (LDH and CK-MB), homocysteine, and inflammatory markers (TNF and CRP). These changes were ameliorated with the administration of atorvastatin and fish oil. HCD increased the levels of nitric oxide synthase and VCAM, while the administration of fish oil improved these markers. Conclusions: Fish oil effectively ameliorates hypercholesterolemia-induced dyslipidemia and inhibits inflammatory biomarkers. Additionally, it lowers cardiac biomarkers, potentially reducing the risk of inflammation, arteriosclerosis, and vascular endothelial dysfunction. These beneficial effects may be attributed to the active components in fish oil. We suggest that fish oils could be used as functional dietary ingredients or supplements to manage the risk of developing CVD. Overall, this study contributes new insights into the biochemical relationships between lipid metabolism, inflammation, and vascular health, while providing a comparative evaluation of fish oil versus atorvastatin in cardiovascular protection.