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Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model

BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA) in Alzheimer’s disease (AD), the mechanism by which DHA affects amyloid-β precursor protein (AβPP)-induced metabolic changes has not been studied. OBJECTIVE: To...

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Autores principales: Bahety, Priti, Tan, Yee Min, Hong, Yanjun, Zhang, Luqi, Chan, Eric Chun Yong, Ee, Pui-Lai Rachel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937442/
https://www.ncbi.nlm.nih.gov/pubmed/24587236
http://dx.doi.org/10.1371/journal.pone.0090123
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author Bahety, Priti
Tan, Yee Min
Hong, Yanjun
Zhang, Luqi
Chan, Eric Chun Yong
Ee, Pui-Lai Rachel
author_facet Bahety, Priti
Tan, Yee Min
Hong, Yanjun
Zhang, Luqi
Chan, Eric Chun Yong
Ee, Pui-Lai Rachel
author_sort Bahety, Priti
collection PubMed
description BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA) in Alzheimer’s disease (AD), the mechanism by which DHA affects amyloid-β precursor protein (AβPP)-induced metabolic changes has not been studied. OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes) associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS). METHODS: The lysate and supernatant samples of CHO-wt and CHO-AβPP(695) cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software. RESULTS: Both principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment. CONCLUSION: Our study shows that DHA plays a role in mitigating AβPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AβPP(695) cells shed further mechanistic insights on its neuroprotective actions.
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spelling pubmed-39374422014-03-04 Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model Bahety, Priti Tan, Yee Min Hong, Yanjun Zhang, Luqi Chan, Eric Chun Yong Ee, Pui-Lai Rachel PLoS One Research Article BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA) in Alzheimer’s disease (AD), the mechanism by which DHA affects amyloid-β precursor protein (AβPP)-induced metabolic changes has not been studied. OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes) associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS). METHODS: The lysate and supernatant samples of CHO-wt and CHO-AβPP(695) cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software. RESULTS: Both principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment. CONCLUSION: Our study shows that DHA plays a role in mitigating AβPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AβPP(695) cells shed further mechanistic insights on its neuroprotective actions. Public Library of Science 2014-02-27 /pmc/articles/PMC3937442/ /pubmed/24587236 http://dx.doi.org/10.1371/journal.pone.0090123 Text en © 2014 Bahety et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bahety, Priti
Tan, Yee Min
Hong, Yanjun
Zhang, Luqi
Chan, Eric Chun Yong
Ee, Pui-Lai Rachel
Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model
title Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model
title_full Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model
title_fullStr Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model
title_full_unstemmed Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model
title_short Metabotyping of Docosahexaenoic Acid - Treated Alzheimer’s Disease Cell Model
title_sort metabotyping of docosahexaenoic acid - treated alzheimer’s disease cell model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937442/
https://www.ncbi.nlm.nih.gov/pubmed/24587236
http://dx.doi.org/10.1371/journal.pone.0090123
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