Modulatory Role of PYY in Transport and Metabolism of Cholesterol in Intestinal Epithelial Cells
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Post-publication record
- Nature
- Retraction
- Reason
- Concerns/Issues about Data;Concerns/Issues about Image;Duplication of/in Image;Investigation by Journal/Publisher;Objections by Third Party;Original Data and/or Images not Provided and/or not Available;
- Date
- 4/14/2022 0:00
- Flagged by OpenAlex?
- Yes
Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.
Abstract
BACKGROUND: Gastrointestinal peptides are involved in modulating appetite. Other biological functions attributed to them include the regulation of lipid homeostasis. However, data concerning PYY remain fragmentary. The objectives of the study were: (i) To determine the effect of PYY on intestinal transport and synthesis of cholesterol, the biogenesis of apolipoproteins (apos) and assembly of lipoproteins and (ii) To analyze whether the effects of PYY are similar according to whether cells are exposed to PYY on apical or basolateral surface. METHODOLOGY/PRINCIPAL FINDINGS: Caco-2/15 cells were incubated with PYY (1-36) administered either to the apical or basolateral medium, at concentrations of 50 or 200 nM for 24 hours. De novo synthesis of cholesterol, cholesterol uptake, and assembly of lipoproteins were evaluated through the incorporation of [(14)C]-acetate, [(14)C]-cholesterol, and [(14)C]-oleate, respectively. Biogenesis of apos (A-I, A-IV, E, B-48 and B-100) was examined by the incorporation of [(35)S]-methionine. The influence of PYY on protein and mRNA levels of many key mediators of lipid metabolism was analyzed by Western blot and PCR, respectively. Our results show that PYY influenced cholesterol metabolism in Caco-2/15 cells depending on the site of PYY delivery. Apical addition of PYY significantly lowered the incorporation of [(14)C]-cholesterol likely via the reduction of NPC1L1, stimulated intracellular cholesterol synthesis probably through an increase in SREBP-2 expression, whereas it concomitantly increased apo A-I synthesis and decreased LDL secretion. In contrast, basolateral PYY reduced the production of chylomicrons (CM) as well as the biogenesis of apos B-48 and B-100, while lowering the expression of the transcription factors RXRα and PPAR(α,β). CONCLUSIONS/SIGNIFICANCE: PYY is capable of influencing cholesterol homeostasis in intestinal Caco-2/15 cells depending on the site delivery. Apical PYY was able to decrease cholesterol uptake via NPC1L1 downregulation, whereas basolateral PYY diminished CM output through the biogenesis decline of apos B-48 and B-100.
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The record
- Venue
- PLoS ONE
- Topic
- Protein Hydrolysis and Bioactive Peptides
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Université de MontréalCentre Hospitalier Universitaire Sainte-Justine
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Keywords
- MetabolismCholesterolCell biologyIntestinal epitheliumEndocrinologyChemistryBiologyInternal medicineEpitheliumMedicineGenetics
- Has abstract in OpenAlex
- yes