Regulation of glucagon-like peptide-1 (GLP-1) by milk protein fractions: an in vitro analysis

Obesity and diabetes are metabolic syndrome associated diseases. Increased body weight has been noticed worldwide and the World Health Organization (WHO) considers this as an epidemic. Reduction in body weight helps to reduce obesity-related issues such as diabetes, fatty liver diseases and certain type of cancers. Stimulating the release of satiety regulation hormones, such as Glucagon-like peptide-1(GLP-1) has been shown to reduce food intake and help with weigh loss. Dietary supplementation with milk proteins has been suggested to be an effective approach to the prevention and treatment of obesity in humans. Other than milk, green tea has also been shown beneficial effect on body weight management. However, the precise mechanisms by which these beneficial effects are mediated are not fully understood.<br><br>This research focuses on new areas for the management of obesity and discusses the possibility of using milk proteins and its fraction and epigallocatechin-3-gallate (EGCG) from green tea, to regulate appetite by stimulating the secretion of GLP-1. EGCG conjugates with Apo-lactoferrin (Apo-LF) were synthesized and the effect on GLP-1 studied, to determine if this combination might have a synergistic effect on the hormone production. Human colorectal (NCI-H716) cell line was used as the model cell line to study the effects of the test substances on GLP-1.<br><br>The results indicate that, with β-casein showing the greatest effect on GLP-1 up regulation at gene and protein levels, with the least toxicity. The interaction between Apo-LF and EGCG in the conjugates was characterized and it was found to be via hydrogen bonding, with a decreased in α-helix of Apo-LF and parallel increase in β sheets. The thermodynamic parameters suggest the interaction is spontaneous, involving hydrophobic forces at ambient temperature and electrostatic forces above 40 ºC. With regards to toxic effects on the cells, the conjugates showed an increase in cell death with decrease in EGCG concentration. This could be due to the smaller EGCG molecule being up taken into the LF molecule at higher concentrations, whereas it remains on the surface of the protein at lower concentrations. Further, the conjugates have a higher effect on enhancing of the expression of GLP-1 compared with pristine Apo-LF and EGCG alone and their effect on the regulation of satiety hormones. In conclusion, the Apo-LF-EGCG conjugates shows potential as a new therapy for the management of obesity, by regulation of satiety hormones.