A Dairy-Derived Ghrelinergic Hydrolysate Modulates Food Intake In Vivo

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.

Milk Exosomal miR-27b Worsen Endoplasmic Reticulum Stress Mediated Colorectal Cancer Cell Death

“…In LoVo and HT-29 cells, 3 kDa milk induced variation in mitochondrial stability initiated by excessive ROS accumulation [ 16 ]. Of note, when we investigated the role of 3 kDa milk in the miR-27b + cell death mechanism(s), results showed that it enhances the apoptosis and ER-stress induction, in line with previous studies showing synergism among milk bioactive compounds [ 15 , 68 , 69 , 70 ]. In addition, as for lactose intolerant consumers, while previous studies reported that ultrafiltration membrane technology decreased the lactose content of milk [ 71 ], a complete depletion of lactose can be achieved by enzymatic approach.…”

Beneficial Impact of Pork Dry-Cured Ham Consumption on Blood Pressure and Cardiometabolic Markers in Individuals with Cardiovascular Risk

“…Further research regarding the role of the CV protective effect of ghrelin would be of great help, including the lowering of BP, the regulation of atherosclerosis, and insulin resistance [46][47][48]. An interesting study recently reported ghrelin-stimulating bioactive peptides derived from casein with potent effects in rats and in vitro [49]. In accordance with our clinical data, another animal study also revealed a decrease in BP after ghrelin administration [50].…”

Role of Bioactive Peptide Sequences in the Potential Impact of Dairy Protein Intake on Metabolic Health

“…To this end, the authors remarked the expression of GHSR-1a on vagal nerve terminals throughout the small and large intestine. In summary, although further studies are required to better characterize a peptide-mediated ghrelinergic bioactivity in casein hydrolysates, we may remark that the two main milk protein fractions, caseins and whey proteins, can release factors upon digestion which show quite opposite effects on the ghrelinergic system and hence on mechanisms regulating hunger [ 144 ].…”