University of Limerick
Browse
Barreto_2022_Integrated.pdf (4.59 MB)

Integrated metabolomics and lipidomics reveal high accumulation of glycerophospholipids in human astrocytes under the lipotoxic effect of palmitic acid and tibolone protection

Download (4.59 MB)
journal contribution
posted on 2022-03-01, 12:01 authored by Ricardo Cabezas, Cynthia Martin-Jiménez, Martha Zuluaga, Andrés Pinzón, George E. Barreto, Janneth González
Lipotoxicity is a metabolic condition resulting from the accumulation of free fatty acids in non-adipose tissues which involves a series of pathological responses triggered after chronic exposure to high levels of fatty acids, severely detrimental to cellular homeostasis and viability. In brain, lipotoxicity affects both neurons and other cell types, notably astrocytes, leading to neurodegenerative processes, such as Alzheimer (AD) and Parkinson diseases (PD). In this study, we performed for the first time, a whole lipidomic characterization of Normal Human Astrocytes cultures exposed to toxic concentrations of palmitic acid and the protective compound tibolone, to establish and identify the set of potential metabolites that are modulated under these experimental treatments. The study covered 3843 features involved in the exo- and endo-metabolome extracts obtained from astrocytes with the mentioned treatments. Through multivariate statistical analysis such as PCA (principal component analysis), partial least squares (PLS-DA), clustering analysis, and machine learning enrichment analysis, it was possible to determine the specific metabolites that were affected by palmitic acid insult, such as phosphoethanolamines, phosphoserines phosphocholines and glycerophosphocholines, with their respective metabolic pathways impact. Moreover, our results suggest the importance of tibolone in the generation of neuroprotective metabolites by astrocytes and may be relevant to the development of neurodegenerative processes.

History

Publication

International Journal of Molecular Sciences;23 (5), 2474

Publisher

MDPI

Note

peer-reviewed

Other Funding information

Pontificia Universidad Javeriana, Bogotá, CTO 654-2020

Language

English

Usage metrics

    University of Limerick

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC