Jiehui Zhou:
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Protein and protein hydrolysates reduce subsequent food intake, but the active components and the associated pathways have not been clearly identified. This study aimed to identify bioactive compounds in meat-derived protein hydrolysates that induce satiety as shown by reduced feed intake. Intestinal cell lines were screened for response, measured as a rise in free cytosolic calcium, to meat-derived hydrolysates a well as purified fractions from hydrolysates. An octapeptide (DC7-2) derived from muscle α-actinin-2 was identified. It has four amino acids identical to neurotensin (NT), an anorexigenic neuropeptide and a gut hormone released from enteroendocrine cells following a meal. A core pentapeptide (KPYIL) lacking the three Nterminal amino acids of DC7-2 was identified to be sufficient for activity. Selective antagonists for the NT receptor (NTR) dose-dependently blocked the ability of DC7-2 and NT to induce a rise in free cytosolic calcium, indicating that binding to and signalling via NTR is responsible for the cell signal. Intraperitoneal and oral administration of DC7-2 reduced feed intake in mice over a period of six hours. This acute effect was associated with an almost immediate effect on gastric emptying following intraperitoneal and oral administration. The in vivo effects on gastric emptying were also blocked by administration of NT antagonists. DC7-2 is stable in the stomach but not in intestine, however, DC7-2 could be protected by non-specific peptides and specific inhibitors from enzymatic degradation. Thus, DC7-2 is a novel meat-derived peptide identified by our cell screening assay, which acutely reduces feed intake in mice at least in part by delaying gastric emptying, which is mediated via NTR. Other compounds, which are able to stimulate cells with nanomolar potency and therefore have potential anti-obesity properties, have also been detected and identified by similar methods.