Investigations on the hypocholesterolaemic activity of LILPKHSDAD and LTFPGSAED, two peptides from lupin β-conglutin: Focus on LDLR and PCSK9 pathways

Zanoni, Chiara; Aiello, Gilda; Arnoldi, Anna; Lammi, Carmen

doi:10.1016/j.jff.2017.02.009

Cited by 52 publications

(79 citation statements)

References 39 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aims of this study were: (1) to develop fast, sensitive, and accurate DPP-IV assays either in situ on human intestinal cells or ex vivo on human serum, using a fluorescent substrate and the specific DPP-IV inhibitor sitagliptin, and (2) to validate the assay on previously identified soy and lupin peptides with known DPP-IV inhibitory activity. In particular, two peptides were chosen: one deriving from lupin beta-conglutin precursor, Lup1 (LTFPGSAED), also named P7 [ 20 , 21 ], and the second from soy glycinin, Soy1 (IAVPTGVA) [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Soybean- and Lupin-Derived Peptides Inhibit DPP-IV Activity on In Situ Human Intestinal Caco-2 Cells and Ex Vivo Human Serum

Lammi

Bollati

Ferruzza³

et al. 2018

Nutrients

Self Cite

View full text Add to dashboard Cite

Recent investigations have focused on food-derived peptides as novel natural inhibitors of dipeptidyl peptidase IV (DPP-IV), a new target for diabetes. This study aimed to optimize fast, sensitive, and cost-effective DPP-IV assays in situ on human intestinal Caco-2 cells and ex vivo on human serum. Both assays were applied to investigate the inhibitory activity of soy and lupin peptides. The best conditions for in situ DPP-IV activity in Caco-2 cells were obtained using 2-day cells and 50 µM Gly-Pro-AMC. Sitagliptin, used as reference inhibitor, showed a dose-dependent response with a 50% inhibition concentration (IC50) of 0.6 µM. A lower IC50 (0.2 µM) was obtained for sitagliptin on human serum incubated with the substrate for 24 h. Both assays were applied to assess the activity of Lup1 (LTFPGSAED) and Soy1 (IAVPTGVA) on DPP-IV. Lup1 and Soy1 inhibited DPP-IV in situ, with IC50 values of of 207.5 and 223.2 µM, respectively, and maintained their inhibitory activity ex vivo on circulating DPP-IV with a slightly lower potency. These assays can be used to characterize the DPP-IV inhibitory activity of food-derived molecules more accurately than in vitro biochemical tests. This combined approach also considers their effects on the circulating form of DPP-IV, correlated to metabolic diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Soybean- and Lupin-Derived Peptides Inhibit DPP-IV Activity on In Situ Human Intestinal Caco-2 Cells and Ex Vivo Human Serum

Lammi

Bollati

Ferruzza³

et al. 2018

Nutrients

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the framework of a research aimed at identifying the molecular mechanism through which lupin peptides are able to mediate a hypocholesterolemic effect in vitro, the main findings of this investigation were the following: (a) the identification of P3 as a new peptide able to inhibit the HMGCoAR activity and to modulate the cholesterol metabolism at hepatic level, (b) the assessment that this ability does not take place via the activation of the SREBP‐2 pathway, as it happens in the case of other lupin peptides (Zanoni, Aiello, Arnoldi, & Lammi, ), but instead via the activation of the SREBP‐1 pathway.…”

Section: Discussionmentioning

confidence: 99%

“…This permitted the identification of some potential inhibitors of this enzyme. Indeed, the first two candidates that were synthesized and investigated, that is, P5 and P7 , resulted to be inhibitors of the HMGCoAR activity with IC 50 values equal to 147.2 ± 1.34 and 68.4 ± 1.53 µM, respectively (Zanoni et al, ). This article, instead, is focused on the activity of a third peptide, that is, P3 .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, this mechanism of modulation of the cholesterol metabolism is also new among the hypocholesterolemic peptides derived from lupin protein. In fact, P 5 and P7 induce the up‐regulation of the LDLR protein level and activity through the SREBP‐2 pathway activation (Zanoni et al, ). Moreover, in contrast with P5 and P7 , P3 is not able to induce an up‐regulation of the AMPK‐ pathway, leading to a stabilization of the SREBP‐1 activity (Figure a–f).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

YDFYPSSTKDQQS (P3), a peptide from lupin protein, absorbed by Caco-2 cells, modulates cholesterol metabolism in HepG2 cells via SREBP-1 activation

et al. 2018

Self Cite

View full text Add to dashboard Cite

YDFYPSSTKDQQS (P3) is a peptide derived from the hydrolysis of lupin protein with pepsin that may be bioavailable, since it is absorbed in Caco-2 cells. In the framework of a research aimed at identifying new hypocholesterolemic peptides from plant proteins, this work provides evidence that P3 inhibits in vitro the functionality of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoAR) and reports the characterization of the molecular mechanism through which this peptide modulates cholesterol metabolism in HepG2 cells. Specifically, through the inhibition of HMGCoAR activity, P3 improves the low density lipoprotein receptor protein levels via SREBP-1 activation, leading to a better ability of HepG2 cells to uptake extracellular low density lipoproteins with a final in vitro hypocholesterolemic effect. Practical applicationsPlant proteins have many practical applications in human nutrition, since they are environmentally sustainable and provide useful health benefits mostly in the area of hypercholesterolemia prevention. The identification of novel bioavailable hypocholesterolemic peptides and the characterization of their mechanism of action may strengthen the awareness of the role of plant proteins in human health. The mechanism through which P3 exerts its hypocholesterolemic activity is distinctive in respect to other plant peptides. Hypocholesterolemic peptides from plant proteins may be included in dietary supplements. K E Y W O R D Sbioavailable peptide, Caco-2 cells, hypocholesterolemic peptide, low density lipoproteins, lupin protein, Lupinus albus, plant protein, SREBP-1 activation

show abstract

“…In vitro, lupin peptide P5 (LILPKHSDAD) and T9 (GDEQSHQDEGVIVR) can inhibit the binding between PCSK9 and LDLR and enhance LDL uptake in HepG2 cells in vitro (Lammi, Zanoni, Aiello, Vistoli, et al ). The authors also reported that the LILPKHSDAD and LTFPGSAED lupin peptides display hypocholesterolemic activity that is focused on the LDLR and PCSK9 pathways in HepG2 cells in vitro (Zanoni, Aiello, Arnoldi, & Lammi, ).…”

Section: Hypocholesterolemic Action Of Peptidesmentioning

confidence: 99%

Structure-function properties of hypolipidemic peptides

Nagaoka

2018

J Food Biochem

View full text Add to dashboard Cite

This review addresses the structure-function properties of hypolipidemic peptides. The cholesterol-lowering peptide (lactostatin: IIAEK) operates via a new regulatory pathway in the calcium-channel-related mitogen-activated protein kinase (MAPK) signaling pathway of cholesterol degradation. The bile acid binding peptide (soystatin, VAWWMY) inhibits the micellar solubility of cholesterol in vitro and cholesterol absorption in vivo. VVYP is the most effective peptide having hypotriglyceridemic action in globin digests. The suppressive effect of globin digest on postprandial hyperlipidemia has been reported in humans. The ability of peptides (KRES, Apolipoprotein A-I mimetic peptides) to interact with lipids, remove LOOH and activate antioxidant enzymes associated with high-density lipoprotein determines their anti-inflammatory and anti-atherogenic properties. The b-conglycinin derived peptides KNPQLR, EITPEKNPQLR, and RKQEEDEDEE QQRE inhibit fatty acid synthase in vitro. These promising findings indicate the need for more conclusive molecular, cellular, and animal and human studies to design innovative new peptides that ameliorate cholesterol and lipid metabolism. Practical applicationsPrevention and amelioration of hypercholesterolemia by dietary regulation are important. Dietary protein and peptides are very useful as regulators of serum cholesterol concentration. Diets low in saturated fat and cholesterol that include soy protein may reduce the risk of heart disease. In Japan, the concept of "food for specified health use" has been introduced for the prevention and treatment of life-style related disease. Thus, peptides derived from food proteins and sources other than food proteins such as peptide-rich functional foods and nutraceutical products, have considerable potential to prevent lifestyle-related diseases, especially hyperlipidemia, as discussed in this review. Furthermore, various strategies have been used for the efficient screening, development, and application of new hypolipidemic peptides. These include the use of phage display (for antiobesity peptide), peptide mimetics (for anti-atherogenic peptide), and molecular targets such as CYP7A1 (for hypocholesterolemic peptide) and prohibitin (for anti-obesity peptide).

show abstract

Investigations on the hypocholesterolaemic activity of LILPKHSDAD and LTFPGSAED, two peptides from lupin β-conglutin: Focus on LDLR and PCSK9 pathways

Cited by 52 publications

References 39 publications

Soybean- and Lupin-Derived Peptides Inhibit DPP-IV Activity on In Situ Human Intestinal Caco-2 Cells and Ex Vivo Human Serum

Soybean- and Lupin-Derived Peptides Inhibit DPP-IV Activity on In Situ Human Intestinal Caco-2 Cells and Ex Vivo Human Serum

YDFYPSSTKDQQS (P3), a peptide from lupin protein, absorbed by Caco-2 cells, modulates cholesterol metabolism in HepG2 cells via SREBP-1 activation

Structure-function properties of hypolipidemic peptides

Contact Info

Product

Resources

About