Abstract
Increased triglyceride, cholesterol, and low-density lipoprotein (LDL) levels cause hyperlipidemia. Despite the availability of statin-based drugs to reduce LDL levels, additional effective treatments for reducing blood lipid concentrations are required. Herein, soybean hydrolysate prepared via peptic and tryptic hydrolysis promoted trans-intestinal cholesterol excretion (TICE) by increasing ATP-binding cassette subfamily G member 5 (ABCG5) and ABCG8 expression. The peptide sequence capable of promoting TICE was determined via HPLC and LC-MS/MS. Based on this, pure artificial peptides were synthesized, and the efficacy of the selected peptides was verified using cellular and hyperlipidemic mouse models. Soybean hydrolysates, including two bioactive peptides (ALEPDHRVESEGGL and SLVNNDDRDSYRLQSGDAL), promoted TICE via the expression of ABCG5 and ABCG8 in enterocytes. They downregulated expression of hepatic cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1 via expression of fibroblast growth factor 19 (FGF19) in a liver X receptor α (LXRa)-dependent pathway. Administration of bioactive peptides to hyperlipidemic mouse models by oral gavage reduced cholesterol levels in serum via upregulation of ABCG5 and ABCG8 expression in the proximal intestine and through fecal cholesterol excretion, upregulated FGF 15/19 expression, and suppressed hepatic bile acid synthesis. Oral administration of soybean-derived bioactive peptides elicited hypolipidemic effects by increasing TICE and decreasing hepatic cholesterol synthesis.
Highlights
Publisher’s Note: MDPI stays neutralHyperlipidemia is characterized by the elevated circulation of very low-density and low-density lipoprotein cholesterol (VLDL-C and LDL-C) and decreased circulation of highdensity lipoprotein cholesterol (HDL-C) in the blood
In the case of atherosclerosis, inordinate circulation of LDL-C is associated with atherosclerotic lesions, whereas decreased circulation of LDL-C delays the development of atherosclerosis [2]
We demonstrated that two specific soybean-derived peptides could upregulate trans-intestinal cholesterol excretion (TICE)
Summary
Hyperlipidemia is characterized by the elevated circulation of very low-density and low-density lipoprotein cholesterol (VLDL-C and LDL-C) and decreased circulation of highdensity lipoprotein cholesterol (HDL-C) in the blood. It is closely correlated with obesity and a sequence of cardiometabolic syndrome which includes hypertension and heart disease [1]. HDL particles play an essential role in the antiatherosclerotic effect through acceptance of cholesterol and its transfer to the liver. HDL has an anti-oxidative role through the oxidation of LDL particles, and prevents the formation of atheroma in the sub-endothelial region [3].
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