Abstract
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.
Highlights
The potential health benefits of the bioactive fragments which exist within the matrix of many food and dietary components have long been known [1]
The apparent success of oral delivery of the bioactive peptide relative to injection may be reflective of the distribution of the growth hormone secretagogue receptor-type 1a (GHSR-1a) in vivo, which is heavily expressed in the gastrointestinal tract and involved in neuronal signalling to appetite centres in the brain [26]
In vivo preclinical studies with this bioactive peptide show its potential to act as an appetite stimulant after oral administration
Summary
The potential health benefits of the bioactive fragments which exist within the matrix of many food and dietary components have long been known [1]. Milk is one of the richest sources of bioactive fragments and there is a growing body of evidence that these can have positive effects on appetite and metabolism [2,3,4,5]. Many of these bioactives are proven to have various health benefits, spanning the digestive, endocrine, cardiovascular, immune and nervous systems [6,7]. More translational studies are required to provide insights into the merits and mechanisms of milk-derived bioactives to treat appetite-related disorders
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