954 SERUM LEVELS OF CHOLESTEROL PRECURSORS AND PLANT STEROLS INDICATE DECREASED INTESTINAL CHOLESTEROL ABSORPTION BUT INCREASED CHOLESTEROL SYNTHESIS IN CAUCASIAN INDIVIDUALS DEVELOPING GALLSTONES

2010 ◽  
Vol 52 ◽  
pp. S369
Author(s):  
M. Krawczyk ◽  
J.F. Miquel ◽  
D. Lütjohann ◽  
R. Schirin-Sokhan ◽  
F. Lammert
Keyword(s):  
Cholesterol Synthesis ◽  
Serum Levels ◽  
Cholesterol Absorption ◽  
Plant Sterols ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Precursors

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.

Molecular Insights into the Mechanisms Underlying the Cholesterol- Lowering Effects of Phytosterols

2019 ◽  
Vol 26 (37) ◽  
pp. 6704-6723 ◽  
Author(s):  
Lídia Cedó ◽  
Marta Farràs ◽  
Miriam Lee-Rueckert ◽  
Joan Carles Escolà-Gil
Keyword(s):  
Bile Acids ◽  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Plant Sterols ◽  
Intestinal Lumen ◽  
Low Density ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Lowering

Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma Low-Density Lipoprotein-Cholesterol (LDL-C) levels when given 2 g/day. Since this dose has not been reported to cause health-related side effects in long-term human studies, food products containing these plant compounds are used as potential therapeutic dietary options to reduce LDL-C and cardiovascular disease risk. Several mechanisms have been proposed to explain the cholesterol-lowering action of phytosterols. They may compete with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption. Recent evidence indicates that phytosterols may also regulate other pathways. Impaired intestinal cholesterol absorption is usually associated with reduced cholesterol transport to the liver, which may reduce the incorporation of cholesterol into Very-Low- Density Lipoprotein (VLDL) particles, thereby lowering the rate of VLDL assembly and secretion. Impaired liver VLDL production may reduce the rate of LDL production. On the other hand, significant evidence supports a role for plant sterols in the Transintestinal Cholesterol Excretion (TICE) pathway, although the exact mechanisms by which they promote the flow of cholesterol from the blood to enterocytes and the intestinal lumen remains unknown. Dietary phytosterols may also alter the conversion of bile acids into secondary bile acids, and may lower the bile acid hydrophobic/hydrophilic ratio, thereby reducing intestinal cholesterol absorption. This article reviews the progress to date in research on the molecular mechanisms underlying the cholesterol-lowering effects of phytosterols.

Plasma Non-cholesterol Sterols as Markers of Cholesterol Synthesis and Intestinal Absorption: A Critical Review

2020 ◽  
Vol 26 (40) ◽  
pp. 5152-5162
Author(s):  
Eder Carlos Rocha Quintão
Keyword(s):  
Intestinal Absorption ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Plasma Concentrations ◽  
Cholesterol Absorption ◽  
Population Based ◽  
Whole Body ◽  
Intestinal Lumen ◽  
Intestinal Cholesterol Absorption ◽  
Artery Disease

Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively. The method aims at replacing initial research procedures such as the use of stable isotopes associated with fecal steroid balance, which are limited by the high cost and tedious procedures. However, we show in this review that numerous results obtained with serum sterol measurements are contradictory. In this regard, the following points are discussed: 1) how phytosterols relate to atherosclerosis considering that defects in biliary output or in the transport of phytosterols from the intestinal mucosa back into the intestinal lumen provide increased content of phytosterols and other sterols in plasma and tissues, thus not allowing to conclude that their presence in arteries and atheromas represents the etiology of atherosclerosis; 2) serum non-cholesterol sterols as markers of cholesterol synthesis and absorption, such as cholestanol, present discrepant results, rendering them often inadequate to identify cases of coronary artery disease as well as alterations in the whole body cholesterol metabolism; 3) such methods of measurement of cholesterol metabolism are confounded by factors like diabetes mellitus, body weight and other pathologies including considerable hereditary hyperlipidemias biological variabilities that influence the efficiency of synthesis and intestinal absorption of cholesterol.

Metabolic and genetic factors modulating subject specific LDL-C responses to plant sterol therapy1This article is an invited review for the Journal's Made In Canada section. The authors gratefully acknowledge the training that was acquired at the Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba. We would specifically like to thank Dr. Peter Jones for his mentorship and significant contribution to the research contained within this manuscript.

2012 ◽  
Vol 90 (5) ◽  
pp. 509-514 ◽  
Author(s):  
Todd C. Rideout ◽  
Scott V. Harding ◽  
Dylan S. Mackay
Keyword(s):  
Plant Sterol ◽  
Disease Risk ◽  
Current Knowledge ◽  
Cardiovascular Disease Risk ◽  
Cholesterol Absorption ◽  
Plant Sterols ◽  
Lipid Lowering ◽  
Clear Understanding ◽  
Significant Heterogeneity ◽  
Intestinal Cholesterol Absorption

Reducing intestinal cholesterol absorption with plant sterol consumption is a well-characterized strategy to lower LDL-C and potentially reduce cardiovascular disease risk. However, over 50 years of clinical research demonstrate that there is significant heterogeneity in the individual LDL-C lowering response to plant sterol therapy. A clear understanding of why plant sterols work effectively in some individuals but not in others will ensure optimal integration of plant sterols in future personalized nutritional lipid-lowering strategies. This review will examine the current knowledge base surrounding the metabolic and genetic determinants of LDL-C lowering in response to plant sterol consumption.

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