ArticleMolecules (Basel, Switzerland)2026
Release of Bioactive Peptides from Whey Protein During In Vitro Digestion and Their Effect on CCK Secretion in Enteroendocrine Cells: An In Silico and In Vitro Approach.
Article in Molecules (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
During gastrointestinal digestion, dietary proteins are hydrolyzed into peptides and free amino acids that modulate enteroendocrine function and satiety-related hormone secretion along the gut-brain axis, thereby contributing to obesity prevention. We investigated whey protein concentrate (WPC) as a source of bioactive peptides and evaluated the effects of its digests on cholecystokinin (CCK) secretion in STC-1 enteroendocrine cells by integrating the standardized INFOGEST in vitro digestion protocol, peptidomics (LC-MS/MS), and in silico bioactivity prediction. In STC-1 cells, the <3 kDa intestinal peptide fraction exhibited the strongest CCK stimulation, positioning these low-molecular-weight peptides as promising bioactive components for satiety modulation and metabolic health applications. Peptidomic analysis of this fraction identified short sequences derived primarily from β-lactoglobulin (β-La) and α-lactalbumin (α-La), enriched in hydrophobic and aromatic residues, including neuropeptide-like sequences containing the Glu-Asn-Ser-Ala-Glu-Pro-Glu (ENSAEPE) motif of β-La f(108-114). In silico bioactivity profiling with MultiPep predicted antihypertensive, angiotensin-converting enzyme (ACE)-inhibitory, antidiabetic, dipeptidyl peptidase-IV (DPP-IV)-inhibitory, antioxidant, antibacterial, and neuropeptide-like activities. Overall, digestion of WPC released low-molecular-weight peptides and amino acids that enhanced CCK secretion in vitro; these findings support their potential use in nutritional strategies to enhance satiety, modulate appetite and energy intake, and improving cardiometabolic health.
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