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 ≤1k Da flaxseed peptide (FP₅ ) reduces cholesterol absorption and synthesis in vitro. In this research, we investigate 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 LC-ESI-Orbitrap MS. 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 (HMGCR, LDLR, CYP7A1, NPC1L1, ABCG5, and ABCG8). 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 re-absorption of bile acids during enterohepatic circulation.