Hypolipidemic and Hypoglycemic Activity of Goat Milk–Derived Peptides

Abstract

The prevalence of diabetes and hyperlipidemia worldwide has increased in recent decades. This study aimed to investigate the potential hypoglycemic and hypolipidemic effects of bioactive peptides derived from goat milk in vitro. Screening of membrane-separated components via Western blot revealed that those with the molecular weight of <1 kDa significantly elevated glucagon-like peptide 1 receptor (GLP-1R) protein expression by nearly 2-fold and low-density lipoprotein receptor (LDLR) protein expression by approximately 3-fold in HepG2 cells, indicating their effective hypoglycemic and lipid-lowering properties. The goat milk–derived peptides were separated and purified utilizing gel chromatography and mass spectrometry. Goat milk–derived bioactive peptide amino acid sequences were determined to obtain Ile–Ala–Ser–Ala–Leu–Pro–Thr–Val–His (IASAEPTVH), Leu–Ser–Thr–Ser–Glu–Glu–Asn–Ser–Lys–Lys (LSTSEENSKK), and Thr–Glu–Asp–Glu–Leu–Gln–Asp–Lys (TEDELQDK) peptides. The toxic effects of IASAEPTVH, LSTSEENSKK, and TEDELQDK on HepG2 cells were negligible, reflecting their excellent biocompatibility. IASAEPTVH, LSTSEENSKK, and TEDELQDK significantly upregulated the expression of GLP-1R and LDLR in a dose-dependent manner. These peptides exhibited considerable inhibitory activity against α-glucosidase. When HepG2 cells were treated with IASAEPTVH, LSTSEENSKK, and TEDELQDK at a concentration of 400 µM, the highest inhibitory activities against α-glucosidase were observed, with inhibitory rates of 76.18% ± 2.10%, 71.94% ± 2.00%, and 70.54% ± 1.76%, respectively. Furthermore, IASAEPTVH, LSTSEENSKK, and TEDELQDK (50–400 µM) suppressed lipid accumulation and reduced triglyceride content in palmitic acid (PA)-overloaded HepG2 cells. In conclusion, goat milk–derived bioactive peptides IASAEPTVH, LSTSEENSKK, and TEDELQDK exerted favorable hypolipidemic and hypoglycemic properties.