Flaxseed‐derived peptide, IPPF, inhibits intestinal cholesterol absorption in Caco‐2 cells and hepatic cholesterol synthesis in HepG2 cells

2021 ◽  
Author(s):  
Xiaolan Bao ◽  
Xingyu Yuan ◽  
Xuexin Li ◽  
Xiaojing Liu
Keyword(s):  
Hepg2 Cells ◽  
Cholesterol Synthesis ◽  
Cholesterol Absorption ◽  
Hepatic Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Hepatic Cholesterol Synthesis

scholarly journals Flaxseed-Derived Peptide, IPPF, Inhibits Intestinal Cholesterol Absorption and Hepatic Cholesterol Synthesis in Caco-2 and HepG2 Cells

2021 ◽  
Author(s):  
Xiaolan Bao ◽  
yuan xingyu ◽  
Xuexin Li ◽  
Xiaojing Liu
Keyword(s):  
Amino Acid ◽  
Hepg2 Cells ◽  
Cholesterol Synthesis ◽  
Cholesterol Absorption ◽  
Amino Acid Sequences ◽  
Hepatic Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Lowering ◽  
Hepatic Cholesterol Synthesis ◽  
Caco2 Cells

Abstract Background：Flaxseed peptide (FPs) showed serum cholesterol-lowering activity in SD rats fed a high-cholesterol diet, but the cholesterol-lowering amino acid sequences and mechanism of FPs were still unclear. Methods: FPs were separated via ultrafiltration, and the amino acid sequences of the selected fractions were determined via high-performance liquid chromatography- Electrospray Ionisation - Orbitrap- Mass spectrometry (HPLC-ESI-Orbitrap MS). These peptides then were synthesized by solid-phase synthesis (SPPS). IPPF with the highest CMSR was determined to exist in flaxseed protein by specific antibodies. The effects of IPPF on intestinal cholesterol absorption and hepatic cholesterol metabolism were investigated in Caco-2 cells and HepG2 cells.Results：1 kDa FP5 fraction had the highest cholesterol micelle solubility inhibition rate (CMSR) 72.39% compared with the other ultrafiltration fractions. Then Eleven peptides were identified from FP5. Ile-Pro-Pro-Phe (IPPF), with the highest CMSR 93.47%, was selected to research the cholesterol-lowering mechanism in Caco-2 and HepG2 cells. IPPF significantly reduces the amount of cholesterol transported in Caco2 cells and the amount of total cholesterol in HepG2 cells. IPPF significantly modulated the protein levels of NCP1L1 and ABCG5/8 in Caco2 cells and significantly reduced the mRNA levels of Srebp-2 and Hmgcr in HepG2 cells. Conclusion: IPPF inhibits cholesterol intestinal absorption through modulating the expression of cholesterol transporters in Caco-2 cells and reduces hepatic cholesterol synthesis through inhibiting the SREBP2-regulated mevalonate (HMGCR) pathway in HepG2 cells. IPPF is a new food-derived inhibitor of intestinal cholesterol absorption and hepatic cholesterol synthesis without side effects and provides a nutritional therapy component for hypercholesterolemia.

scholarly journals Modulating Sterol Concentrations in Infant Formula Influences Cholesterol Absorption and Synthesis in the Neonatal Piglet

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1848 ◽  
Author(s):  
Elizabeth Babawale ◽  
Peter Jones ◽  
Kelly Mercer ◽  
Haixia Lin ◽  
Laxmi Yeruva ◽  
...  
Keyword(s):  
Human Milk ◽  
Cholesterol Synthesis ◽  
Cholesterol Absorption ◽  
Infant Formulas ◽  
Feeding Period ◽  
Hepatic Cholesterol ◽  
Inhibitory Effects ◽  
Hepatic Cholesterol Synthesis ◽  
Cholesterol Levels ◽  
Breast Fed

Formula-fed infants present higher cholesterol synthesis rates and lower circulating cholesterol during the postnatal feeding period compared to breast-fed infants, though the mechanisms underlying this phenotype are not fully understood. Typical infant formulas contain vegetable-based fats, inherently including phytosterols (PS), which are structurally similar to cholesterol and may interfere with their absorption. A seven-day old piglets model was used to test the inhibitory effects of PS on cholesterol absorption during postnatal feeding. Following feeding for 21 days with milk-based formulas containing PS and cholesterol levels resembling those in formulas or human-milk, apparent cholesterol digestibility was analyzed in ileal digesta, and cholesterol, PS, and cholesterol synthesis markers were analyzed in plasma and liver samples. Ileal cholesterol digestibility content was increased in the piglets fed low PS formulas and the rate of the hepatic cholesterol synthesis, as determined by the lathosterol-to-cholesterol ratios (L:C), was decreased in the piglets fed LP-formulas and corresponded to reduced nuclear expression of SREBP2 relative to those fed HP-formulas. These results are consistent with the hypothesis that PS in formula can inhibit cholesterol absorption and enhance cholesterol synthesis. Whether or not this leads to entrainment of cholesterol synthesis later in life via early programming awaits further research.

scholarly journals Mechanisms of cholesterol-lowering effects of dietary insoluble fibres: relationships with intestinal and hepatic cholesterol parameters

2005 ◽  
Vol 94 (3) ◽  
pp. 331-337 ◽  
Author(s):  
Ariëtte M. van Bennekum ◽  
David V. Nguyen ◽  
Georg Schulthess ◽  
Helmut Hauser ◽  
Michael C. Phillips
Keyword(s):  
Bile Acid ◽  
Food Intake ◽  
Serum Cholesterol ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
Hepatic Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Lowering ◽  
Dietary Fibres ◽  
Bile Acid Binding

Fibres with a range of abilities to perturb cholesterol homeostasis were used to investigate how the serum cholesterol-lowering effects of insoluble dietary fibres are related to parameters of intestinal cholesterol absorption and hepatic cholesterol homeostasis in mice. Cholestyramine, chitosan and cellulose were used as examples of fibres with high, intermediate and low bile acid-binding capacities, respectively. The serum cholesterol levels in a control group of mice fed a high fat/high cholesterol (HFHC) diet for 3 weeks increased about 2-fold to 4·3 mm and inclusion of any of these fibres at 7·5 % of the diet prevented this increase from occurring. In addition, the amount of cholesterol accumulated in hepatic stores due to the HFHC diet was reduced by treatment with these fibres. The three kinds of fibres showed similar hypocholesterolaemic activity; however, cholesterol depletion of liver tissue was greatest with cholestyramine. The mechanisms underlying the cholesterol-lowering effect of cholestyramine were (1) decreased cholesterol (food) intake, (2) decreased cholesterol absorption efficiency, and (3) increased faecal bile acid and cholesterol excretion. The latter effects can be attributed to the high bile acid-binding capacity of cholestyramine. In contrast, incorporation of chitosan or cellulose in the diet reduced cholesterol (food) intake, but did not affect either intestinal cholesterol absorption or faecal sterol output. The present study provides strong evidence that above all satiation and satiety effects underlie the cholesterol-lowering properties of insoluble dietary fibres with moderate or low bile acid-binding capabilities.

Increased hepatic cholesterol synthesis in normal rats by cross-circulation with ileal bypassed partners

1979 ◽  
Vol 34 (4) ◽  
pp. 383-389 ◽  
Author(s):  
Philip D. Schneider ◽  
Ignacio J. Guzman ◽  
Richard D. Rucker ◽  
Thomas G. Stocks ◽  
Richard L. Varco ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis

Selective effects of two novel squalene synthase inhibitors on hepatic cholesterol synthesis in the rat

1994 ◽  
Vol 109 (1-2) ◽  
pp. 252 ◽  
Author(s):  
G.J. Smith ◽  
R.G. Davidson ◽  
C. Dunkley ◽  
G.R. Brown ◽  
K.B. Mallion ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Squalene Synthase ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis ◽  
Selective Effects
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