Plasma from obese children increases monocyte-endothelial adhesion and affects intracellular insulin signaling in cultured endothelial cells: Potential role of mTORC1-S6K1.
Autor: | Di Pietrantonio N; Department of Medical, Oral and Biotechnological Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy., Palmerini C; Department of Medical, Oral and Biotechnological Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy., Pipino C; Department of Medical, Oral and Biotechnological Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy., Baldassarre MPA; Department of Medicine and Aging Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy., Bologna G; Department of Medicine and Aging Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy., Mohn A; Pediatrics Division, Hospital SS. Annunziata, Chieti, Italy., Giannini C; Department of Medicine and Aging Sciences, Italy; Pediatrics Division, Hospital SS. Annunziata, Chieti, Italy., Lanuti P; Department of Medicine and Aging Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy., Chiarelli F; Department of Medicine and Aging Sciences, Italy; Pediatrics Division, Hospital SS. Annunziata, Chieti, Italy., Pandolfi A; Department of Medical, Oral and Biotechnological Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy., Di Pietro N; Department of Medical, Oral and Biotechnological Sciences, Italy; Center for Advanced Studies and Technology - CAST (ex CeSI-MeT), University G. d'Annunzio of Chieti-Pescara, Italy. Electronic address: n.dipietro@unich.it. |
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Jazyk: | angličtina |
Zdroj: | Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2021 Apr 01; Vol. 1867 (4), pp. 166076. Date of Electronic Publication: 2021 Jan 08. |
DOI: | 10.1016/j.bbadis.2021.166076 |
Abstrakt: | Childhood obesity is characterized by the loss of vascular insulin sensitivity along with altered oxidant-antioxidant state and chronic inflammation, which play a key role in the onset of endothelial dysfunction. We previously demonstrated a reduced insulin-stimulated Nitric Oxide (NO) bioavailability in Human Umbilical Vein Endothelial cells (HUVECs) cultured with plasma from obese pre-pubertal children (OB) compared to those cultured with plasma of normal-weight children (CTRL). However, mechanisms underlying endothelial dysfunction in childhood obesity remains poorly understood. Hence, the present study aimed to better investigate these mechanisms, also considering a potential involvement of mammalian Target Of Rapamycin Complex1 (mTORC1)-ribosomal protein S6 Kinase beta1 (S6K1) pathway. OB-children (N = 32, age: 9.2 ± 1.7; BMI z-score: 2.72 ± 0.31) had higher fasting insulin levels and increased HOMA-IR than CTRL-children (N = 32, age: 8.8 ± 1.2; BMI z-score: 0.33 ± 0.75). In vitro, HUVECs exposed to OB-plasma exhibited significant increase in Reactive Oxygen Species (ROS) levels, higher vascular and intercellular adhesion molecules exposure, together with increased monocytes-endothelial interaction. This was associated with unbalanced pro- and anti-atherogenic endothelial insulin stimulated signaling pathways, as measured by increased Mitogen Activated Protein Kinase (MAPK) and decreased Insulin Receptor Substrate-1 (IRS-1)/protein kinase B (Akt)/ endothelial NO Synthase (eNOS) phosphorylation levels, together with augmented S6K1 activation. Interestingly, inhibition of mTORC1-S6K1 pathway using rapamycin significantly restored the IRS-1/Akt/eNOS activation, suggesting a feedback regulation of IRS-1/Akt signal through S6K1. Overall, our in vitro data shed light on new mechanisms underlying the onset of endothelial dysfunction in childhood obesity. (Copyright © 2021 Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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