Intestinal alkaline phosphatase is a receptor for cholesterol-lowering pentapeptide IIAEK and regulates cholesterol homeostasis in mice.

ABSTRACT: Dietary proteins are absorbed by the intestine as amino acids or peptides. Di- or tripeptides are absorbed via the intestinal peptide transporter 1 (PepT1); however, the intestinal target of oligopeptides larger than tetrapeptides remain unclear, posing a major contradiction in the current protein-peptide nutrition. This study aimed to explore the unidentified function of intestinal alkaline phosphatase (IAP) in regulating cholesterol metabolism using the dietary peptide IIAEK. In IAP-knockout (Akp3^-/-) mice, the IIAEK-induced amelioration of cholesterol metabolism via the suppression of intestinal cholesterol absorption was absent. Furthermore, we found that IIAEK specifically interacts with the substrate recognition sites of mouse IAP (Akp3) and human IAP. The IIAEK-human IAP

SUBMITTER: Takeuchi A 

PROVIDER: S-EPMC12217679 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature