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Blood cholesterol balance is regulated by an interplay between the small intestine and the liver. Recently, a new protein (cholesin) was discovered, which is secreted by intestinal cells after dietary cholesterol intake. Cholesin travels to the liver and binds to the GPR146 receptor. This inhibits cholesterol production in the liver. Because plant sterols lower blood cholesterol levels by reducing cholesterol absorption in the intestine, the investigators would like to understand the effects of plant sterols on GPR146. The investigator hypothesis is that the production of the GPR146 gene differs after adding plant sterols to a high-cholesterol diet compared to eating a high-cholesterol and low-cholesterol diet. The main objective of this study is to investigate whether the expression of the GPR146 gene in the blood of adults differs between three meals with different levels of cholesterol intake. The secondary objective of the study is to examine changes in the expression of cholesin, the LDL receptor (LDLR), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) genes in the blood after these meals. Furthermore, changes in the expression of these genes, all of which play an important role in cholesterol metabolism, will be examined in intestinal cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cholesterol-poor, plant sterol-poor shake | Active Comparator | Participants will be given a mixed meal in the form of a cholesterol-poor, plant-sterol-poor shake. |
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| Cholesterol-rich, plant sterol-poor shake | Active Comparator | Participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-poor shake. |
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| Cholesterol-rich plant sterol-rich shake | Experimental | Participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-rich shake. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cholesterol-poor, plant sterol-poor shake | Dietary Supplement | The first arm is the cholesterol-poor arm, where participants will be given a mixed meal in the form of a cholesterol-poor, plant-sterol-poor shake which provides the lowest cholesterol absorption rate. |
| Measure | Description | Time Frame |
|---|---|---|
| The postprandial changes in GPR146 gene expression in peripheral blood mononuclear cells (PBMCs) after three dietary conditions. | The gene expression levels will be determined by messenger RNA (mRNA) quantification using the real-time reverse transcription polymerase chain reaction (RT-qPCR) method in PBMCs and reported as fold change (increase or decrease) relative to baseline. | At baseline (fasting; before the meal) and at 360 minutes (6-hours) postprandial |
| Measure | Description | Time Frame |
|---|---|---|
| The postprandial changes in C7orf50, HMGCR, and LDLR gene expressions in peripheral blood mononuclear cells (PBMCs) after three dietary conditions. | The gene expression levels will be determined by messenger RNA (mRNA) quantification using the real-time reverse transcription polymerase chain reaction (RT-qPCR) method in PBMCs and reported as fold change (increase or decrease) relative to baseline |
| Measure | Description | Time Frame |
|---|---|---|
| The changes in small intestinal mucosal cells gene expression profiles of GPR146, C7orf50, HMGCR, and LDLR genes after the three meals | The gene expression levels will be determined by messenger RNA (mRNA) quantification using the real-time reverse transcription polymerase chain reaction (RT-qPCR) method in small intestinal biopsy samples. | 6-hours postprandial |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jogchum Plat, PhD | Contact | +31-43-3881309 | j.plat@maastrichtuniversity.nl | |
| Dena Nuwaylati, MD, MSc | Contact | +31-433881599 | dena.nuwaylati@maastrichtuniversity.nl |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University | Maastricht | Limburg | 6229 ER | Netherlands |
Due to data protection and participants' confidentiality, this will be decided by the principal investigator based on a reasonable request.
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| Cholesterol-rich, plant sterol-poor shake | Dietary Supplement | The second arm is the high-cholesterol arm, where participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-poor shake, which provides the highest cholesterol absorption rate. |
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| Cholesterol-rich, plant sterol-rich shake | Dietary Supplement | The third arm is the moderate-cholesterol arm, where participants will be given a mixed meal in the form of a cholesterol-rich, plant-sterol-rich shake, which provides the moderate cholesterol absorption rate. |
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| At baseline (fasting; before the meal) and at 360 minutes (6-hours) postprandial |
| The postprandial changes in GPR146 and LDLR protein expressions in peripheral blood mononuclear cells after three dietary conditions. | The protein expression levels will be measured by fluorescence-activated cell sorting (FACS) analysis and reported as percentage of marker-positive cells and/or fold change in mean fluorescence intensity from baseline. | At baseline (fasting; before the meal) and at 360 minutes (6-hours) postprandial |
| The postprandial response of serum triacylglycerol (TAG) and apolipoprotein B-48 (apoB-48) to the three meals | Serum TAG will be measured spectrophotometrically, and apoB-48 will be quantified by enzyme-linked immunosorbent assay (ELISA) | At intervals of 7 time-points during the postprandial period (0-6 hours) |