Novel Hypocholesterolemic Peptides Derived from Silver Carp Muscle: The Modulatory Effects on Enterohepatic Cholesterol Metabolism In Vitro and In Vivo

被引:6
作者
Wang, Kai [3 ]
Han, Lihua [3 ]
Tan, Yuqing [3 ]
Hong, Hui [3 ]
Fan, Hongbing [4 ]
Luo, Yongkang [1 ,2 ]
机构
[1] China Agr Univ, Coll Food Sci & Nutr Engn, Beijing Lab Food Qual & Safety, Beijing 100083, Peoples R China
[2] Jiangxi Normal Univ, Natl Res & Dev Ctr Freshwater Fish Proc, Nanchang 330022, Jiangxi, Peoples R China
[3] China Agr Univ, Coll Food Sci & Nutr Engn, Beijing Lab Food Qual & Safety, Beijing 100083, Peoples R China
[4] Univ Kentucky, Dept Anim & Food Sci, Lexington, KY 40546 USA
关键词
silver carp muscle hydrolysate; cholesterol absorption; LDL uptake; hypercholesterolemia mice; transepithelial transport; peptide sequences; SIMULATED GASTROINTESTINAL DIGESTION; ENZYME-INHIBITORY PEPTIDES; HEPG2; CELLS; PROTEIN; EXPRESSION; PCSK9; IDENTIFICATION; REGULATORS; STEROL; NPC1L1;
D O I
10.1021/acs.jafc.2c09092
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
This research aimed to investigate the effect of silver carp hydrolysates (SCHs) on hypercholesterolemia and enterohepatic cholesterol metabolism. Results showed that in vitro gastrointestinal digestion products of Alcalase-SCH (GID-Alcalase) exhibited the highest inhibitory activity of cholesterol absorption mainly through downregulating the expression of essential genes related to cholesterol transport in a Caco-2 monolayer. After being absorbed by the Caco-2 monolayer, GID-Alcalase increased the low-density lipoprotein (LDL) uptake in HepG2 cells by enhancing the protein level of the LDL receptor (LDLR). The in vivo experiment showed that long-term intervention of Alcalase-SCH ameliorated hypercholesterolemia in ApoE-/- mice fed with a Western diet (WD). After transepithelial transport, four novel peptides (TKY, LIL, FPK, and IAIM) were identified, and these peptides possessed dual hypocholesterolemic functions including inhibition of cholesterol absorption and promotion of peripheric LDL uptake. Our results indicated for the first time the potential of SCHs as functional food ingredients for the management of hypercholesterolemia.
引用
收藏
页码:5565 / 5575
页数:11
相关论文
共 40 条
[1]   Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: role of sterol regulatory element binding protein 2 [J].
Alrefai, Waddah A. ;
Annaba, Fadi ;
Sarwar, Zaheer ;
Dwivedi, Alka ;
Saksena, Seema ;
Singla, Amika ;
Dudeja, Pradeep K. ;
Gill, Ravinder K. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2007, 292 (01) :G369-G376
[2]   Identification of a novel cholesterol-lowering dipeptide, phenylalanine-proline (FP), and its down-regulation of intestinal ABCA1 in hypercholesterolemic rats and Caco-2 cells [J].
Banno, Arata ;
Wang, Jilite ;
Okada, Kenji ;
Mori, Ryosuke ;
Mijiti, Maihemuti ;
Nagaoka, Satoshi .
SCIENTIFIC REPORTS, 2019, 9 (1)
[3]   Effect of protein hydrolysates from sardinelle (Sardinella aurita) on the oxidative status and blood lipid profile of cholesterol-fed rats [J].
Ben Khaled, Hayet ;
Ghlissi, Zohra ;
Chtourou, Yassine ;
Hakim, Ahmed ;
Ktari, Naourez ;
Fatma, Makni Ayadi ;
Barkia, Ahmed ;
Sahnoun, Zouheir ;
Nasri, Moncef .
FOOD RESEARCH INTERNATIONAL, 2012, 45 (01) :60-68
[4]   Modulation of LDL receptor expression and promoter methylation in HepG2 cells treated with a Corylus avellana L. extract [J].
Benassi, Barbara ;
Santi, Chiara ;
Santangelie, Stefania ;
Grollino, Maria Giuseppa ;
Raschella, Giuseppe ;
Bacchetta, Loretta ;
Pacchierotti, Francesca .
JOURNAL OF FUNCTIONAL FOODS, 2019, 53 :208-218
[5]   From amino acid sequence to bioactivity: The biomedical potential of antitumor peptides [J].
Blanco-Miguez, Aitor ;
Gutierrez-Jacome, Alberto ;
Perez-Perez, Martin ;
Perez-Rodriguez, Gael ;
Catalan-Garcia, Sandra ;
Fdez-Riverola, Florentino ;
Lourenco, Analia ;
Sanchez, Borja .
PROTEIN SCIENCE, 2016, 25 (06) :1084-1095
[6]   Molecular mechanisms of cholesterol-lowering peptides derived from food proteins [J].
Boachie, Ruth ;
Yao, Shixiang ;
Udenigwe, Chibuike C. .
CURRENT OPINION IN FOOD SCIENCE, 2018, 20 :58-63
[7]   INFOGEST static in vitro simulation of gastrointestinal food digestion [J].
Brodkorb, Andre ;
Egger, Lotti ;
Alminger, Marie ;
Alvito, Paula ;
Assuncao, Ricardo ;
Ballance, Simon ;
Bohn, Torsten ;
Bourlieu-Lacanal, Claire ;
Boutrou, Rachel ;
Carriere, Frederic ;
Clemente, Alfonso ;
Corredig, Milena ;
Dupont, Didier ;
Dufour, Claire ;
Edwards, Cathrina ;
Golding, Matt ;
Karakaya, Sibel ;
Kirkhus, Bente ;
Le Feunteun, Steven ;
Lesmes, Uri ;
Macierzanka, Adam ;
Mackie, Alan R. ;
Martins, Carla ;
Marze, Sebastien ;
McClements, David Julian ;
Menard, Olivia ;
Minekus, Mans ;
Portmann, Reto ;
Santos, Claudia N. ;
Souchon, Isabelle ;
Singh, R. Paul ;
Vegarud, Gerd E. ;
Wickham, Martin S. J. ;
Weitschies, Werner ;
Recio, Isidra .
NATURE PROTOCOLS, 2019, 14 (04) :991-1014
[8]   Investigations into inhibitor type and mode, simulated gastrointestinal digestion, and cell transport of the angiotensin I-Converting enzyme-inhibitory peptides in pacific hake (Merluccius productus) fillet hydrolysate [J].
Cinq-Mars, Crystal D. ;
Hu, Chun ;
Kitts, David D. ;
Li-Chan, Eunice C. Y. .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2008, 56 (02) :410-419
[9]   Niemann-Pick C1 like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis [J].
Davis, HR ;
Zhu, LJ ;
Hoos, LM ;
Tetzloff, G ;
Maguire, M ;
Liu, JJ ;
Yao, XR ;
Iyer, SPN ;
Lam, MH ;
Lund, EG ;
Detmers, PA ;
Graziano, MP ;
Altmann, SW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (32) :33586-33592
[10]   Strong induction of PCSK9 gene expression through HNF1α and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters [J].
Dong, Bin ;
Wu, Minhao ;
Li, Hai ;
Kraemer, Fredric B. ;
Adeli, Khosrow ;
Seidah, Nabil G. ;
Park, Sahng Wook ;
Liu, Jingwen .
JOURNAL OF LIPID RESEARCH, 2010, 51 (06) :1486-1495