Flaxseed-derived peptides ameliorate hepatic cholesterol metabolism in Sprague-Dawley rats fed a high-cholesterol and high-fat diet.

Abstract

Background: Plant peptides have been reported to have cholesterol-lowering activities. Previous research has found that ≤1 kDa flaxseed peptide (FP₅ ) reduces cholesterol absorption and synthesis in vitro. In this research, we investigated the cholesterol-lowering activity of FP₅ in Sprague-Dawley (SD) rats fed a high-cholesterol and high-fat diet. In addition, amino acid sequences of FP₅ were determined by high-performance liquid chromatography-electrospray ionization-Orbitrap mass spectrometry. Results: FP₅ supplement significantly decreased the serum and hepatic cholesterol levels and modulated the hepatic gene and protein expression of cholesterol metabolism-related enzymes or regulators (3-hydroxy-3-methylglutaryl coenzyme A reductase, Low-Density Lipoprotein Receptor (LDLR), Cholesterol 7 α-hydroxylase, Niemann-Pick C1-like 1, ATP-binding cassette transporters G5 and G8). Eleven peptides were identified from FP₅. These peptides were characterized as hydrophobic amino acids such as leucine (L), proline (P), glycine (G), isoleucine (I) and continuous sequences, including LP, LL, LG and II, with low molecular weights. Conclusion: FP₅ has a certain cholesterol-lowering activity in SD rats fed a high-cholesterol and high-fat diet. The possible mechanism for ameliorating hepatic cholesterol metabolism of FP₅ includes inhibiting hepatic cholesterol de novo synthesis, promoting the synthesis and excretion of bile acids, and inhibiting the reabsorption of bile acids during enterohepatic circulation.