Integrated metabolomics and lipidomics reveal high accumulation of glycerophospholipids in human astrocytes under the lipotoxic effect of palmitic acid and tibolone protection
posted on 2022-03-01, 12:01authored byRicardo 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