Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways

Abstract The pathophysiological actions of fatty acids (FAs) on Alzheimer’s disease (AD), which are possibly mediated by genomic effects, are widely known; however, their non-genomic actions remain elusive. The aim of this study was to investigate the non-genomic mechanism of extra-cellular palmitic...

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Autores principales:	Jeong Yeon Kim, Hyun Jik Lee, Sei-Jung Lee, Young Hyun Jung, Dae Young Yoo, In Koo Hwang, Je Kyung Seong, Jung Min Ryu, Ho Jae Han
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8c72c87da4a49d0be11b7b42cd21a28
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spelling	oai:doaj.org-article:c8c72c87da4a49d0be11b7b42cd21a282021-12-02T15:05:15ZPalmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways10.1038/s41598-017-04175-w2045-2322https://doaj.org/article/c8c72c87da4a49d0be11b7b42cd21a282017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04175-whttps://doaj.org/toc/2045-2322Abstract The pathophysiological actions of fatty acids (FAs) on Alzheimer’s disease (AD), which are possibly mediated by genomic effects, are widely known; however, their non-genomic actions remain elusive. The aim of this study was to investigate the non-genomic mechanism of extra-cellular palmitic acid (PA) regulating beta-amyloid peptide (Aβ) production, which may provide a link between obesity and the occurrence of AD. In an obese mouse model, a high-fat diet (HFD) significantly increased the expression levels of APP and BACE1 as well as the AD pathology in the mouse brain. We further found that PA conjugated with bovine serum albumin (PA-BSA) increased the expression of APP and BACE1 and the production of Aβ through the G protein-coupled receptor 40 (GPR40) in SK-N-MC cells. PA-BSA coupling with GPR40 significantly induced Akt activation which is required for mTOR/p70S6K1-mediated HIF-1α expression and NF-κB phosphorylation facilitating the transcriptional activity of the APP and BACE1 genes. In addition, silencing of APP and BACE1 expression significantly decreased the production of Aβ in SK-N-MC cells treated with PA-BSA. In conclusion, these results show that extra-cellular PA coupled with GPR40 induces the expression of APP and BACE1 to facilitate Aβ production via the Akt-mTOR-HIF-1α and Akt-NF-κB pathways in SK-N-MC cells.Jeong Yeon KimHyun Jik LeeSei-Jung LeeYoung Hyun JungDae Young YooIn Koo HwangJe Kyung SeongJung Min RyuHo Jae HanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeong Yeon Kim Hyun Jik Lee Sei-Jung Lee Young Hyun Jung Dae Young Yoo In Koo Hwang Je Kyung Seong Jung Min Ryu Ho Jae Han Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways
description	Abstract The pathophysiological actions of fatty acids (FAs) on Alzheimer’s disease (AD), which are possibly mediated by genomic effects, are widely known; however, their non-genomic actions remain elusive. The aim of this study was to investigate the non-genomic mechanism of extra-cellular palmitic acid (PA) regulating beta-amyloid peptide (Aβ) production, which may provide a link between obesity and the occurrence of AD. In an obese mouse model, a high-fat diet (HFD) significantly increased the expression levels of APP and BACE1 as well as the AD pathology in the mouse brain. We further found that PA conjugated with bovine serum albumin (PA-BSA) increased the expression of APP and BACE1 and the production of Aβ through the G protein-coupled receptor 40 (GPR40) in SK-N-MC cells. PA-BSA coupling with GPR40 significantly induced Akt activation which is required for mTOR/p70S6K1-mediated HIF-1α expression and NF-κB phosphorylation facilitating the transcriptional activity of the APP and BACE1 genes. In addition, silencing of APP and BACE1 expression significantly decreased the production of Aβ in SK-N-MC cells treated with PA-BSA. In conclusion, these results show that extra-cellular PA coupled with GPR40 induces the expression of APP and BACE1 to facilitate Aβ production via the Akt-mTOR-HIF-1α and Akt-NF-κB pathways in SK-N-MC cells.
format	article
author	Jeong Yeon Kim Hyun Jik Lee Sei-Jung Lee Young Hyun Jung Dae Young Yoo In Koo Hwang Je Kyung Seong Jung Min Ryu Ho Jae Han
author_facet	Jeong Yeon Kim Hyun Jik Lee Sei-Jung Lee Young Hyun Jung Dae Young Yoo In Koo Hwang Je Kyung Seong Jung Min Ryu Ho Jae Han
author_sort	Jeong Yeon Kim
title	Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways
title_short	Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways
title_full	Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways
title_fullStr	Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways
title_full_unstemmed	Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways
title_sort	palmitic acid-bsa enhances amyloid-β production through gpr40-mediated dual pathways in neuronal cells: involvement of the akt/mtor/hif-1α and akt/nf-κb pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c8c72c87da4a49d0be11b7b42cd21a28
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Palmitic Acid-BSA enhances Amyloid-β production through GPR40-mediated dual pathways in neuronal cells: Involvement of the Akt/mTOR/HIF-1α and Akt/NF-κB pathways

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