Effect of Linoleic Acid on Cholesterol Levels in a High-Fat Diet-Induced Hypercholesterolemia Rat Model

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, accounting for almost one-third of all deaths. The risk factors for developing this disease include high levels of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), alongside low levels of high-density lipoprotein (HDL). Dietary linoleic acid has been suggested to reduce these risk factors. This study aims to determine the effects of linoleic acid on cholesterol levels, liver function tests, and structural changes in liver tissue in comparison with fenofibrate in a hypercholesterolemic rat model. Thirty-six male Sprague Dawley rats (150-180 g) were divided into non-hypercholesterolemic and hypercholesterolemic groups. Hypercholesterolemia was induced in the rats by feeding them with a high-fat diet for two weeks. After two weeks, the non-hypercholesterolemic and hypercholesterolemic rats were equally divided into six groups (n = 6): control non-hypercholesterolemic rats, non-hypercholesterolemic rats treated with fenofibrate (60 mg/kg), non-hypercholesterolemic rats treated with linoleic acid (5 mg/kg), control hypercholesterolemic rats, hypercholesterolemic rats treated with fenofibrate (60 mg/kg), and hypercholesterolemic rats treated with linoleic acid (5 mg/kg). The changes in the rats' body weight, serum lipid profiles, atherogenic indices, and liver function test results were obtained. The rats' liver tissues were stained for histopathological analysis. The linoleic acid-treated hypercholesterolemic rats exhibited significantly reduced serum TC, TG, LDL, aspartate aminotransferase, and alanine aminotransferase levels, as well as increased HDL levels compared with the control hypercholesterolemic rats. These linoleic acid effects were comparable to those in the fenofibrate-treated hypercholesterolemic rats. In conclusion, linoleic acid possesses early anti-hypercholesterolemic properties, which may be due to the reductions in serum cholesterol levels and mild early structural changes in the liver tissues of hypercholesterolemic rats. Therefore, continued studies on linoleic acid in atherosclerotic and/or obese animal models are suggested.