Department of Integrated Biological Science, Pusan National University, Busan 46241, Korea.
Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea.
Nutrients. 2021 Dec 27;14(1):95. doi: 10.3390/nu14010095.
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.
甘油三酯、胆固醇和低密度脂蛋白（LDL）水平升高会导致高脂血症。尽管有他汀类药物可降低 LDL 水平，但仍需要其他有效的治疗方法来降低血脂浓度。本文中，通过胃蛋白酶和胰蛋白酶水解制备的大豆水解产物通过增加三磷酸腺苷结合盒亚家族 G 成员 5（ABCG5）和 ABCG8 的表达来促进跨肠胆固醇排泄（TICE）。通过 HPLC 和 LC-MS/MS 确定了能够促进 TICE 的肽序列。基于此，合成了纯人工肽，并使用细胞和高脂血症小鼠模型验证了所选肽的功效。大豆水解产物（包括两种生物活性肽 ALEPDHRVESEGGL 和 SLVNNDDRDSYRLQSGDAL）通过肠细胞中 ABCG5 和 ABCG8 的表达促进 TICE。它们通过肝 X 受体 α（LXRa）依赖性途径下调肝微粒体 P450 家族 7 亚家族 A 成员 1（CYP7A1）和 CYP8B1 的表达，同时通过成纤维细胞生长因子 19（FGF19）表达。通过口服给予高脂血症小鼠模型生物活性肽，通过上调近端肠中 ABCG5 和 ABCG8 的表达以及通过粪便胆固醇排泄来降低血清中的胆固醇水平，上调 FGF15/19 的表达，并抑制肝胆汁酸合成。口服大豆衍生的生物活性肽通过增加 TICE 和减少肝内胆固醇合成来发挥降血脂作用。
