Recent times have seen an increasing move towards harnessing the health-promoting benefits of food and dietary constituents while providing scientific evidence to substantiate their claims. In particular, the potential for bioactive
protein hydrolysates and
peptides to enhance health in conjunction with conventional
pharmaceutical therapy is being investigated. Dairy-derived
proteins have been shown to contain bioactive
peptide sequences with various purported health benefits, with effects ranging from the digestive system to cardiovascular circulation, the immune system and the central nervous system. Interestingly, the ability of dairy
proteins to modulate metabolism and appetite has recently been reported. The
ghrelin receptor (GHSR-1a) is a
G-protein coupled receptor which plays a key role in the regulation of food intake. Pharmacological manipulation of the
growth hormone secretagogue receptor-type 1a (GHSR-1a) receptor has therefore received a lot of attention as a strategy to
combat disorders of appetite and
body weight, including age-related
malnutrition and the progressive muscle
wasting syndrome known as
cachexia. In this study, a
milk protein-derivative is shown to increase GHSR-1a-mediated intracellular
calcium signalling in a concentration-dependent manner in vitro. Significant increases in
calcium mobilisation were also observed in a cultured neuronal cell line heterologously expressing the
GHS-R1a. In addition, both additive and synergistic effects were observed following co-exposure of GHSR-1a to both the hydrolysate and
ghrelin. Subsequent in vivo studies monitored standard chow intake in healthy male and female Sprague-Dawley rats after dosing with the
casein hydrolysate (CasHyd). Furthermore, the provision of gastro-protected oral delivery to the bioactive in vivo may aid in the progression of in vitro efficacy to in vivo functionality. In summary, this study reports a
ghrelin-stimulating bioactive
peptide mixture (CasHyd) with potent effects in vitro. It also provides novel and valuable translational data supporting the potential role of CasHyd as an appetite-enhancing bioactive. Further mechanistic studies are required in order to confirm efficacy as a ghrelinergic bioactive in susceptible population groups.