Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells

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.

Casein glycomacropeptide is well tolerated in healthy adults and changes neither high-sensitive C-reactive protein, gut microbiota nor faecal butyrate: a restricted randomised trial

“…Recently, CGMP has been found to exert anti-oxidative and anti-inflammatory effects in a cell model mimicking the oxidative stress, and low-grade inflammation that are characteristics of metabolic syndrome. (76) In conclusion, the present study supports earlier findings that CGMP is safe and well tolerated and has an acceptable palatability and no effects on satiety and body weight. We found neither immunomodulatory effects nor effects on markers of intestinal immune homeostasis in healthy subjects with no signs of inflammation.…”

“…In the future, a safe, palatable protein with anti-inflammatory potential might be of benefit in patients with various degrees of intestinal inflammation, for example, patients with the metabolic syndrome or inflammatory bowel disease. Recently, CGMP has been found to exert anti-oxidative and anti-inflammatory effects in a cell model mimicking the oxidative stress, and low-grade inflammation that are characteristics of the metabolic syndrome (76) .…”

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

“…Although we did not perform permeability assays, we believe that the inhibitory effect of GMP on IL-1β and TNF-α expression and the up-regulation of TGF-β at the intestine of FA animals may prevent an impaired intestinal barrier function, as it has been demonstrated with in vitro studies using cell lines of enterocytes and goblet cells [ 81 , 82 ]. This suggestion is supported by studies showing that GMP is able to inhibit signaling pathways involved in TNF-α and IL-1β gene expression, such as NF-κB and MAPK pathways, in the intestinal mucosa of mice with ulcerative colitis [ 83 ], as well as in cell lines of goblet cells [ 81 ], mature enterocytes [ 84 ], and macrophages [ 85 ]. Future research in this field will be necessary to demonstrate it.…”

<p>Association of Metabolic Syndrome and Hyperferritinemia in Patients at Cardiovascular Risk</p>

“…This condition can progress to cirrhosis, and in about 2 to 3% of patients, hepatocellular carcinoma may occur. [39][40][41][42][43][44] For all these reasons, it is crucial to investigate the ferritin concentration and the MS parameters in patients.…”