Abstract
There has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits. Cattle heart protein hydrolysate ultra-filtrate (HPHU, molecular weight < ca. 1,000 Da peptide mixture) exhibits cholesterol-lowering activity in hypercholesterolemic rats, but the active peptide in HPHU that lowers serum cholesterol levels and its molecular mechanism are unknown. In this study, we separated and purified HPHU to identify a novel cholesterol-lowering dipeptide (phenylalanine-proline, FP) and characterized the mechanism underlying its effects in vivo and in vitro. We identified FP as an active peptide from HPHU by MALDI-TOF mass spectrometry. FP significantly decreased serum total and non-HDL cholesterol and hepatic cholesterol levels in rats. FP significantly increased serum HDL cholesterol, accompanied by a significant decrease in the atherogenic index. FP also significantly increased fecal cholesterol and acidic steroid excretion. Moreover, FP significantly decreased ATP-binding cassette transporter A1 (ABCA1) expression in the rat jejunum and reduced cholesterol absorption in Caco-2 cells. We found a novel cholesterol-lowering dipeptide FP that could improve cholesterol metabolism via the down-regulation of intestinal ABCA1. The cholesterol-lowering action induced by FP was disappeared in PepT1KO mice. FP-induced cholesterol-lowering action is mediated via PepT1 in mice.
Highlights
There has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits
We previously reported that cattle heart protein hydrolysate (HPH) and cattle heart protein hydrolysate ultra-filtrate (HPHU, Molecular weight (MW) < ca. 1,000 Da peptide fraction) exert strong hypocholesterolemic activity in rats[14]
These results suggested that active peptides of HPHU related to the inhibitory effect on cholesterol micellar solubility are concentrated in the gf[3] fraction
Summary
There has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits. We separated and purified HPHU to identify a novel cholesterol-lowering dipeptide (phenylalanine-proline, FP) and characterized the mechanism underlying its effects in vivo and in vitro. FP significantly decreased serum total and non-HDL cholesterol and hepatic cholesterol levels in rats. Increased serum total cholesterol and LDL cholesterol and decreased HDL cholesterol induces hypercholesterolemia, which is a critical risk factor for atherosclerosis and ischemic heart disease[1,2]. Some studies have suggested that dietary proteins, such as soybean protein[11,12] and sunflower protein hydrolysates[13] decrease the micellar solubility of cholesterol in vitro and have hypocholesterolemic actions in animals. Very little is known about specific food-derived peptides that reduce serum cholesterol levels in vivo and more researches are required in this field
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