title: Metabotyping of docosahexaenoic acid - treated Alzheimer's disease cell model.
abstract: 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-AβPP695 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.
  
  
  CONCLUSIONS
  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-AβPP695 cells shed further mechanistic insights on its neuroprotective actions.
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Priti
authors.initials: P
authors.lastname: Bahety
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Yee Min
authors.initials: YM
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Luqi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Eric Chun Yong
authors.initials: EC
authors.lastname: Chan
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Pui-Lai Rachel
authors.initials: PL
authors.lastname: Ee
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004281:Docosahexaenoic Acids / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008401:Gas Chromatography-Mass Spectrometry; D015870:Gene Expression; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome; D055432:Metabolomics; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011768:Pyruvate Dehydrogenase Complex; D004281:Docosahexaenoic Acids