Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells
Background. Metabolic Syndrome (MetS), a major worldwide concern for the public health system, refers to a cluster of key metabolic components, and represents a risk factor for diabetes and cardiovascular diseases. As oxidative stress (OxS) and inflammation are the major triggers of insulin sensitiv...
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MDPI AG
2020-04-01
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author | Mathilde Foisy-Sauvé Lena Ahmarani Edgard Delvin Alain T. Sané Schohraya Spahis Emile Levy |
author_facet | Mathilde Foisy-Sauvé Lena Ahmarani Edgard Delvin Alain T. Sané Schohraya Spahis Emile Levy |
author_sort | Mathilde Foisy-Sauvé |
collection | DOAJ |
description | Background. Metabolic Syndrome (MetS), a major worldwide concern for the public health system, refers to a cluster of key metabolic components, and represents a risk factor for diabetes and cardiovascular diseases. As oxidative stress (OxS) and inflammation are the major triggers of insulin sensitivity (IS), a cardinal MetS feature, the principal aim of the present work is to determine whether glycomacropeptide (GMP), a milk-derived bioactive peptide, exerts beneficial effects on their expression. Methods. Fully differentiated intestinal Caco-2/15 cells are used to evaluate the preventive action of 2 mg/mL GMP against OxS and inflammation induced by the mixture iron-ascorbate (Fe/Asc) (200 μM:2 mM). The potency of GMP of decreasing the production of lipoproteins, including chylomicrons (CM), very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) is also assessed. Results. The administration of GMP significantly reduces malondialdehyde, a biomarker of lipid peroxidation, and raises superoxide dismutase 2 and glutathione peroxidase via the induction of the nuclear factor erythroid 2–related factor 2, a transcription factor, which orchestrates cellular antioxidant defenses. Similarly, GMP markedly lowers the inflammatory agents tumor necrosis factor-α and cyclooxygenase-2 via abrogation of the nuclear transcription factor-kB. Moreover, GMP-treated cells show a down-regulation of Fe/Asc-induced mitogen activated protein kinase pathway, suggesting greater IS. Finally, GMP decreases the production of CM, VLDL, and LDL. Conclusions. Our results highlight the effectiveness of GMP in attenuating OxS, inflammation and lipoprotein biogenesis, as well as improving IS, the key components of MetS. Further investigation is needed to elucidate the mechanisms mediating the preventive action of GMP. |
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spelling | doaj.art-fd17b2b480fa446da9186dc2b108c3412023-11-19T22:25:57ZengMDPI AGNutrients2072-66432020-04-01124117510.3390/nu12041175Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 CellsMathilde Foisy-Sauvé0Lena Ahmarani1Edgard Delvin2Alain T. Sané3Schohraya Spahis4Emile Levy5Research Centre, CHU Ste-Justine, Montreal, QC H3T 1C5, CanadaResearch Centre, CHU Ste-Justine, Montreal, QC H3T 1C5, CanadaResearch Centre, CHU Ste-Justine, Montreal, QC H3T 1C5, CanadaResearch Centre, CHU Ste-Justine, Montreal, QC H3T 1C5, CanadaResearch Centre, CHU Ste-Justine, Montreal, QC H3T 1C5, CanadaResearch Centre, CHU Ste-Justine, Montreal, QC H3T 1C5, CanadaBackground. Metabolic Syndrome (MetS), a major worldwide concern for the public health system, refers to a cluster of key metabolic components, and represents a risk factor for diabetes and cardiovascular diseases. As oxidative stress (OxS) and inflammation are the major triggers of insulin sensitivity (IS), a cardinal MetS feature, the principal aim of the present work is to determine whether glycomacropeptide (GMP), a milk-derived bioactive peptide, exerts beneficial effects on their expression. Methods. Fully differentiated intestinal Caco-2/15 cells are used to evaluate the preventive action of 2 mg/mL GMP against OxS and inflammation induced by the mixture iron-ascorbate (Fe/Asc) (200 μM:2 mM). The potency of GMP of decreasing the production of lipoproteins, including chylomicrons (CM), very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) is also assessed. Results. The administration of GMP significantly reduces malondialdehyde, a biomarker of lipid peroxidation, and raises superoxide dismutase 2 and glutathione peroxidase via the induction of the nuclear factor erythroid 2–related factor 2, a transcription factor, which orchestrates cellular antioxidant defenses. Similarly, GMP markedly lowers the inflammatory agents tumor necrosis factor-α and cyclooxygenase-2 via abrogation of the nuclear transcription factor-kB. Moreover, GMP-treated cells show a down-regulation of Fe/Asc-induced mitogen activated protein kinase pathway, suggesting greater IS. Finally, GMP decreases the production of CM, VLDL, and LDL. Conclusions. Our results highlight the effectiveness of GMP in attenuating OxS, inflammation and lipoprotein biogenesis, as well as improving IS, the key components of MetS. Further investigation is needed to elucidate the mechanisms mediating the preventive action of GMP.https://www.mdpi.com/2072-6643/12/4/1175glycomacropeptideoxidative stressinflammationinsulin sensitivitymetabolic syndromemilk-derived bioactive peptide |
spellingShingle | Mathilde Foisy-Sauvé Lena Ahmarani Edgard Delvin Alain T. Sané Schohraya Spahis Emile Levy Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells Nutrients glycomacropeptide oxidative stress inflammation insulin sensitivity metabolic syndrome milk-derived bioactive peptide |
title | Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells |
title_full | Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells |
title_fullStr | Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells |
title_full_unstemmed | Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells |
title_short | Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells |
title_sort | glycomacropeptide prevents iron ascorbate induced oxidative stress inflammation and insulin sensitivity with an impact on lipoprotein production in intestinal caco 2 15 cells |
topic | glycomacropeptide oxidative stress inflammation insulin sensitivity metabolic syndrome milk-derived bioactive peptide |
url | https://www.mdpi.com/2072-6643/12/4/1175 |
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