Masou salmon (Oncorhynchus masou) ethanol extract decreases 3-hydroxy-3-methylglutaryl coenzyme A reductase expression in diet-induced obese mice

Abstract 

This study was designed to evaluate the hypocholesterolemic effects of masou salmon 70% ethanol extract (MSE) and to determine the molecular mechanism by which MSE exerts its effects in high-fat (HF) diet-induced obese mice. We hypothesize that the MSE may contain abundant n-3 fatty acids, so a diet containing MSE may also have hypolipidemic effects by assessing several key gene expressions in cholesterol metabolism such as the low-density lipoprotein (LDL) receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and cholesterol 7α-hydroxylase (CYP7A1). To test this hypothesis, C57BL/6J mice were fed a 40% HF diet for 5 weeks, after which time the animals were fed an HF diet containing 0 mg/kg, 75 mg/kg, or 150 mg/kg MSE (HF, HF + MSE 1, and HF + MSE 2 groups, respectively) for an additional 4 weeks (n = 8 in each group, for a total of 24 mice). We found that feeding MSE with an HF diet prevented hypercholesterolemia in diet-induced obese mice; daily MSE feeding reduced total cholesterol levels in plasma and liver by 12.3% and 16.2%, respectively. Furthermore, we examined the expression of key cholesterol metabolism genes by reverse transcription-polymerase chain reaction and found that messenger RNA levels of HMG-CoA reductase were decreased by up to 5-fold, but the expression of both LDL receptor and CYP7A1 did not change. Thus, MSE may exert its hypocholesterolemic effect by altering the expression of HMG-CoA reductase.

Abbreviations: CYP7A1, cholesterol 7α-hydroxylase, DHA, docosahexaenoic acid, EPA, eicosapentaenoic acid, FA, fatty acid, HDL, high-density lipoprotein, HF, high-fat, HMG-CoA reductase, 3-hydroxy-3-methylglutaryl-CoA reductase, LDL receptor, low-density lipoprotein receptor, mRNA, messenger RNA, MSE, masou salmon 70% ethanol extract, PCR, polymerase chain reaction, PUFA, polyunsaturated fatty acids

Keywords: Mice, Obese, Hypocholesterolemic effect, HMG-CoA reductase, Cholesterol, Masou salmon