NMR-based metabolomic profile of hypercholesterolemic human sera: Relationship with in vitro gene expression?
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| Abstract |
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.
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| Authors | Manuela Grimaldi, Angelica Palisi, Carmen Marino, Paola Montoro, Anna Capasso, Sara Novi, Mario Felice Tecce, Anna Maria D'Ursi |
| Journal | PloS one (PLoS One) Vol. 15 Issue 4 Pg. e0231506 ( 2020) ISSN: 1932-6203 [Electronic] United States |
| PMID | 32298312 (Publication Type: Journal Article) |
| Chemical References |
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