NMR-based metabolomic profile of hypercholesterolemic human sera: Relationship with in vitro gene expression?

Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs...

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Published in:	PloS one 2020-04, Vol.15 (4), p.e0231506-e0231506
Main Authors:	Grimaldi, Manuela, Palisi, Angelica, Marino, Carmen, Montoro, Paola, Capasso, Anna, Novi, Sara, Tecce, Mario Felice, D'Ursi, Anna Maria
Format:	Article
Language:	eng
Subjects:	Abnormalities Acetates Acetic acid Acetone Arteriosclerosis Atherosclerosis Biological products Biology and Life Sciences Biosynthesis Cardiovascular diseases Cholesterol Citric acid Coenzyme A Comparative analysis Cysteine Data analysis Disease Enzymes Fourier transforms Gene expression Gluconeogenesis Glutamine Glycolysis Hepatoma Hypercholesterolemia Ketone bodies Ketones Medicine and Health Sciences Metabolism Metabolites Metabolomics Mitochondria NMR Nuclear magnetic resonance Pharmacy Physical Sciences Physiological aspects Principal components analysis Pyruvic acid Research and analysis methods RNA Statistical analysis Thiols Valine
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Summary:	Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs related to mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2). In the present work, using an NMR metabolomic analysis, we demonstrate that the hypercholesterolaemic blood sera previously used to treat cultured hepatoma cells are characterized by a metabolomic profile that is significantly different from the normocholesterolaemic sera. Acetate, acetone, 2-hydroxybutyrate, cysteine, valine, and glutamine are the metabolites distinguishing the two groups. Abnormalities in the concentrations of these metabolites reflect alterations in energy-related pathways, such as pantothenate and CoA biosynthesis, pyruvate, glycolysis/gluconeogenesis, the citrate cycle, and ketone bodies. Regarding ketone bodies, the pathway is regulated by HMGCS2; therefore, serum samples previously found to be able to increase HMGCS2 mRNA levels in cultured cells also contain higher amounts of the metabolites of its encoded enzyme protein product.
ISSN:	1932-6203 1932-6203