Serum Starvation Accelerates Intracellular Metabolism in Endothelial Cells

Periods of low energy supply are challenging conditions for organisms and cells during fasting or famine. Although changes in nutrient levels in the blood are first sensed by endothelial cells, studies on their metabolic adaptations to diminished energy supply are lacking. We analyzed the dynamic me...

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Main Authors: Mario Lorenz, Raphaela Fritsche-Guenther, Cornelia Bartsch, Angelika Vietzke, Alina Eisenberger, Karl Stangl, Verena Stangl, Jennifer A. Kirwan
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/2/1189
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author Mario Lorenz
Raphaela Fritsche-Guenther
Cornelia Bartsch
Angelika Vietzke
Alina Eisenberger
Karl Stangl
Verena Stangl
Jennifer A. Kirwan
author_facet Mario Lorenz
Raphaela Fritsche-Guenther
Cornelia Bartsch
Angelika Vietzke
Alina Eisenberger
Karl Stangl
Verena Stangl
Jennifer A. Kirwan
author_sort Mario Lorenz
collection DOAJ
description Periods of low energy supply are challenging conditions for organisms and cells during fasting or famine. Although changes in nutrient levels in the blood are first sensed by endothelial cells, studies on their metabolic adaptations to diminished energy supply are lacking. We analyzed the dynamic metabolic activity of human umbilical vein endothelial cells (HUVECs) in basal conditions and after serum starvation. Metabolites of glycolysis, the tricarboxylic acid (TCA) cycle, and the glycerol pathway showed lower levels after serum starvation, whereas amino acids had increased levels. A metabolic flux analysis with <sup>13</sup>C-glucose or <sup>13</sup>C-glutamine labeling for different time points reached a plateau phase of incorporation after 30 h for <sup>13</sup>C-glucose and after 8 h for <sup>13</sup>C-glutamine under both experimental conditions. Notably, we observed a faster label incorporation for both <sup>13</sup>C-glucose and <sup>13</sup>C-glutamine after serum starvation. In the linear range of label incorporation after 3 h, we found a significantly faster incorporation of central carbon metabolites after serum starvation compared to the basal state. These findings may indicate that endothelial cells develop increased metabolic activity to cope with energy deficiency. Physiologically, it can be a prerequisite for endothelial cells to form new blood vessels under unfavorable conditions during the process of angiogenesis in vivo.
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spelling doaj.art-56e7c98fb29149e7bc6f3159984a14f02023-11-30T22:36:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242118910.3390/ijms24021189Serum Starvation Accelerates Intracellular Metabolism in Endothelial CellsMario Lorenz0Raphaela Fritsche-Guenther1Cornelia Bartsch2Angelika Vietzke3Alina Eisenberger4Karl Stangl5Verena Stangl6Jennifer A. Kirwan7Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, 10117 Berlin, GermanyMetabolomics Platform, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyCharité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, 10117 Berlin, GermanyCharité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, 10117 Berlin, GermanyMetabolomics Platform, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyCharité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, 10117 Berlin, GermanyCharité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, 10117 Berlin, GermanyMetabolomics Platform, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, 10117 Berlin, GermanyPeriods of low energy supply are challenging conditions for organisms and cells during fasting or famine. Although changes in nutrient levels in the blood are first sensed by endothelial cells, studies on their metabolic adaptations to diminished energy supply are lacking. We analyzed the dynamic metabolic activity of human umbilical vein endothelial cells (HUVECs) in basal conditions and after serum starvation. Metabolites of glycolysis, the tricarboxylic acid (TCA) cycle, and the glycerol pathway showed lower levels after serum starvation, whereas amino acids had increased levels. A metabolic flux analysis with <sup>13</sup>C-glucose or <sup>13</sup>C-glutamine labeling for different time points reached a plateau phase of incorporation after 30 h for <sup>13</sup>C-glucose and after 8 h for <sup>13</sup>C-glutamine under both experimental conditions. Notably, we observed a faster label incorporation for both <sup>13</sup>C-glucose and <sup>13</sup>C-glutamine after serum starvation. In the linear range of label incorporation after 3 h, we found a significantly faster incorporation of central carbon metabolites after serum starvation compared to the basal state. These findings may indicate that endothelial cells develop increased metabolic activity to cope with energy deficiency. Physiologically, it can be a prerequisite for endothelial cells to form new blood vessels under unfavorable conditions during the process of angiogenesis in vivo.https://www.mdpi.com/1422-0067/24/2/1189metabolismserum starvationendothelial cellsHUVECflux analysislabeling
spellingShingle Mario Lorenz
Raphaela Fritsche-Guenther
Cornelia Bartsch
Angelika Vietzke
Alina Eisenberger
Karl Stangl
Verena Stangl
Jennifer A. Kirwan
Serum Starvation Accelerates Intracellular Metabolism in Endothelial Cells
International Journal of Molecular Sciences
metabolism
serum starvation
endothelial cells
HUVEC
flux analysis
labeling
title Serum Starvation Accelerates Intracellular Metabolism in Endothelial Cells
title_full Serum Starvation Accelerates Intracellular Metabolism in Endothelial Cells
title_fullStr Serum Starvation Accelerates Intracellular Metabolism in Endothelial Cells
title_full_unstemmed Serum Starvation Accelerates Intracellular Metabolism in Endothelial Cells
title_short Serum Starvation Accelerates Intracellular Metabolism in Endothelial Cells
title_sort serum starvation accelerates intracellular metabolism in endothelial cells
topic metabolism
serum starvation
endothelial cells
HUVEC
flux analysis
labeling
url https://www.mdpi.com/1422-0067/24/2/1189
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AT angelikavietzke serumstarvationacceleratesintracellularmetabolisminendothelialcells
AT alinaeisenberger serumstarvationacceleratesintracellularmetabolisminendothelialcells
AT karlstangl serumstarvationacceleratesintracellularmetabolisminendothelialcells
AT verenastangl serumstarvationacceleratesintracellularmetabolisminendothelialcells
AT jenniferakirwan serumstarvationacceleratesintracellularmetabolisminendothelialcells