Abstract

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.

Highlights

  • The intestine plays an essential role in nutrient digestion and absorption

  • No significant alterations were noted in cell viability using trypan blue staining and MTT assay, as described previously [34] after

  • The health benefits of milk protein compounds are highlighted in many scientific reports, their impact on the gastrointestinal tract has not been investigated even if this system is central in cardiometabolic health homeostasis given its functional, physical, chemical, immunological, and microbiological properties

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Summary

Introduction

The intestine plays an essential role in nutrient digestion and absorption. It actively participates in host protection and metabolism by housing much of the human microbiota [1,2].It exerts a marked influence on health, being equipped with a strong neuroendocrine system, producing a number of centrally and peripherally metabolically effective peptides [3,4,5]. The intestine plays an essential role in nutrient digestion and absorption. It actively participates in host protection and metabolism by housing much of the human microbiota [1,2]. It exerts a marked influence on health, being equipped with a strong neuroendocrine system, producing a number of centrally and peripherally metabolically effective peptides [3,4,5]. 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: mM). GMP decreases the production of CM, VLDL, and LDL

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