A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways

Lupin protein hydrolysates (LPHs) are gaining attention in the food and nutraceutical industries due to their several beneficial health effects. Recently, we have shown that LPH treatment reduces liver cholesterol and triglyceride levels in hypercholesterolemic mice. The aim of this study was to elu...

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Autores: Santos Sanchez, Guillermo, Cruz Chamorro, Iván, Bollati, Carlotta, Bartolomei, Martina, Pedroche, Justo, Millán, Francisco, Millan Linares, Carmen, Carrillo Vico, Antonio, Lammi, Carmen
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/176970
Acceso en línea:https://hdl.handle.net/11441/176970
https://doi.org/10.1039/d1fo03847h
Access Level:acceso abierto
Palabra clave:Lupinus angustifolius protein
diet-fed ApoE−/− mice
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spelling A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathwaysSantos Sanchez, GuillermoCruz Chamorro, IvánBollati, CarlottaBartolomei, MartinaPedroche, JustoMillán, FranciscoMillan Linares, CarmenCarrillo Vico, AntonioLammi, CarmenLupinus angustifolius proteindiet-fed ApoE−/− miceLupin protein hydrolysates (LPHs) are gaining attention in the food and nutraceutical industries due to their several beneficial health effects. Recently, we have shown that LPH treatment reduces liver cholesterol and triglyceride levels in hypercholesterolemic mice. The aim of this study was to elucidate the effects of LPH treatment on the molecular mechanism underlying liver cholesterol metabolism in ApoE−/− mice fed the Western diet. After identifying the composition of the peptide within the LPH mixture and determining its ability to reduce HMGCoAR activity in vitro, its effect on the LDLR and PCSK9 pathways was measured in liver tissue from the same mice. Thus, the LPH reduced the protein levels of HMGCoAR and increased the phosphorylated inactive form of HMGCoAR and the pHMGCoAR/HMGCoAR ratio, which led to the deactivation of de novo cholesterol synthesis. Furthermore, the LPH decreased the protein levels of SREBP2, a key upstream transcription factor involved in the expression of HMGCoAR and LDLR. Consequently, LDLR protein levels decreased in the liver of LPH-treated animals. Interestingly, the LPH also increased the protein levels of pAMPK responsible for HMGCoAR phosphorylation. Furthermore, the LPH controlled the PSCK9 signal pathway by decreasing its transcription factor, the HNF1-α protein. Consequently, lower PSCK9 protein levels were found in the liver of LPH-treated mice. This is the first study elucidating the molecular mechanism at the basis of the hypocholesterolemic effects exerted by the LPH in an in vivo model. All these findings point out LPHs as a future lipid-lowering ingredient to develop new functional foods.Royal society chemistryBioquímica Médica y Biología Molecular e InmunologíaCTS160: Neuroinmunoendocrinología MolecularJunta de AndalucíaGobierno de España2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/176970https://doi.org/10.1039/d1fo03847hreponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésFood & function, 13 (7), 4158-4170.PC-0111-2016-0111DOC_00587/2020https://pubs.rsc.org/en/content/articlelanding/2022/fo/d1fo03847hinfo:eu-repo/semantics/openAccessoai:idus.us.es:11441/1769702026-06-17T12:51:07Z
dc.title.none.fl_str_mv A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
title A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
spellingShingle A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
Santos Sanchez, Guillermo
Lupinus angustifolius protein
diet-fed ApoE−/− mice
title_short A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
title_full A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
title_fullStr A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
title_full_unstemmed A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
title_sort A Lupinus angustifolius protein hydrolysate exerts hypocholesterolemic effects in Western diet-fed ApoE−/− mice through the modulation of LDLR and PCSK9 pathways
dc.creator.none.fl_str_mv Santos Sanchez, Guillermo
Cruz Chamorro, Iván
Bollati, Carlotta
Bartolomei, Martina
Pedroche, Justo
Millán, Francisco
Millan Linares, Carmen
Carrillo Vico, Antonio
Lammi, Carmen
author Santos Sanchez, Guillermo
author_facet Santos Sanchez, Guillermo
Cruz Chamorro, Iván
Bollati, Carlotta
Bartolomei, Martina
Pedroche, Justo
Millán, Francisco
Millan Linares, Carmen
Carrillo Vico, Antonio
Lammi, Carmen
author_role author
author2 Cruz Chamorro, Iván
Bollati, Carlotta
Bartolomei, Martina
Pedroche, Justo
Millán, Francisco
Millan Linares, Carmen
Carrillo Vico, Antonio
Lammi, Carmen
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bioquímica Médica y Biología Molecular e Inmunología
CTS160: Neuroinmunoendocrinología Molecular
Junta de Andalucía
Gobierno de España
dc.subject.none.fl_str_mv Lupinus angustifolius protein
diet-fed ApoE−/− mice
topic Lupinus angustifolius protein
diet-fed ApoE−/− mice
description Lupin protein hydrolysates (LPHs) are gaining attention in the food and nutraceutical industries due to their several beneficial health effects. Recently, we have shown that LPH treatment reduces liver cholesterol and triglyceride levels in hypercholesterolemic mice. The aim of this study was to elucidate the effects of LPH treatment on the molecular mechanism underlying liver cholesterol metabolism in ApoE−/− mice fed the Western diet. After identifying the composition of the peptide within the LPH mixture and determining its ability to reduce HMGCoAR activity in vitro, its effect on the LDLR and PCSK9 pathways was measured in liver tissue from the same mice. Thus, the LPH reduced the protein levels of HMGCoAR and increased the phosphorylated inactive form of HMGCoAR and the pHMGCoAR/HMGCoAR ratio, which led to the deactivation of de novo cholesterol synthesis. Furthermore, the LPH decreased the protein levels of SREBP2, a key upstream transcription factor involved in the expression of HMGCoAR and LDLR. Consequently, LDLR protein levels decreased in the liver of LPH-treated animals. Interestingly, the LPH also increased the protein levels of pAMPK responsible for HMGCoAR phosphorylation. Furthermore, the LPH controlled the PSCK9 signal pathway by decreasing its transcription factor, the HNF1-α protein. Consequently, lower PSCK9 protein levels were found in the liver of LPH-treated mice. This is the first study elucidating the molecular mechanism at the basis of the hypocholesterolemic effects exerted by the LPH in an in vivo model. All these findings point out LPHs as a future lipid-lowering ingredient to develop new functional foods.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/176970
https://doi.org/10.1039/d1fo03847h
url https://hdl.handle.net/11441/176970
https://doi.org/10.1039/d1fo03847h
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Food & function, 13 (7), 4158-4170.
PC-0111-2016-0111
DOC_00587/2020
https://pubs.rsc.org/en/content/articlelanding/2022/fo/d1fo03847h
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal society chemistry
publisher.none.fl_str_mv Royal society chemistry
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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