| Summary: | 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.<span style="text-transform: uppercase;"> </span>Methods.<span style="text-transform: uppercase;"> </span>Fully differentiated <span style="background: white;">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</span>)<span style="background: white;"> (</span>200 μM:2 mM)<span style="background: white;">. 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. </span>Results. <span style="background: white;">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. </span>Conclusions. <span style="background: white;">Our results highlight the effectiveness of GMP in attenuating OxS, inflammation and lipoprotein biogenesis, as well as improving IS, the key</span> components of MetS. Further investigation is needed to elucidate the mechanisms mediating the preventive action of GMP.
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