Metabolomic Analysis Reveals Vitamin D-induced Decrease in Polyol Pathway and Subtle Modulation of Glycolysis in HEK293T Cells

• Published in: Scientific reports Vol. 7; no. 1; pp. 9510 - 13
• Main Authors: Santos, G. C., Zeidler, J. D., Pérez-Valencia, J. A., Sant’Anna-Silva, A. C. B., Da Poian, A. T., El-Bacha, T., Almeida, F. C. L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.08.2017; Nature Publishing Group
• Subjects: 631/1647/320; 631/45/320; 631/80/304; 82/1; 82/29; 82/6; Biosynthesis; Cell Respiration - drug effects; Choline; Electron transport; Embryos; Glucose; Glucose - metabolism; Glycine; Glycolysis; Guanine; HEK293 Cells; Homeostasis; Humanities and Social Sciences; Humans; Hyperglycemia; Lactic acid; Metabolic Networks and Pathways - drug effects; Metabolism; Metabolome - drug effects; Metabolomics; Metabolomics - methods; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Models, Biological; multidisciplinary; NMR; Nuclear magnetic resonance; Oxidative stress; Phosphocholine; Phosphoglycerate mutase; Phosphopyruvate hydratase; Polymers - metabolism; Proton Magnetic Resonance Spectroscopy; Pyrimidines; Science; Science (multidisciplinary); Sorbitol; Tricarboxylic acid cycle; Vitamin D; Vitamin D - pharmacology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-10006-9

We combined 1 H NMR metabolomics with functional and molecular biochemical assays to describe the metabolic changes elicited by vitamin D in HEK293T, an embryonic proliferative cell line adapted to high-glucose concentrations. Activation of the polyol pathway, was the most important consequence of cell exposure to high glucose concentration, resembling cells exposed to hyperglycemia. Vitamin D induced alterations in HEK293T cells metabolism, including a decrease in sorbitol, glycine, glutamate, guanine. Vitamin D modulated glycolysis by increasing phosphoglycerate mutase and decreasing enolase activities, changing carbon fate without changing glucose consumption, lactate export and Krebs cycle. The decrease in sorbitol intracellular concentration seems to be related to vitamin D regulated redox homeostasis and protection against oxidative stress, and helped maintaining the high proliferative phenotype, supported by the decrease in glycine and guanine and orotate concentration and increase in choline and phosphocholine concentration. The decrease in orotate and guanine indicated an increased biosynthesis of purine and pyrimidines. Vitamin D elicited metabolic alteration without changing cellular proliferation and mitochondrial respiration, but reclaiming reductive power. Our study may contribute to the understanding of the metabolic mechanism of vitamin D upon exposure to hyperglycemia, suggesting a role of protection against oxidative stress.