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 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.