Evidence map›Paper›PMID 31589318›Full record

ArticleCardiovascular research2020

Colesevelam enhances the beneficial effects of brown fat activation on hyperlipidaemia and atherosclerosis development.

Enchen Zhou, Geerte Hoeke, Zhuang Li, Arthur C Eibergen, Amber W Schonk, Martijn Koehorst, Renze Boverhof, Rick Havinga, Folkert Kuipers, Tamer Coskun and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
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  8. Sympathetic Nervous System and Atherosclerosis.International journal of molecular sciences · 2023
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  17. Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Enchen ZhouDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Geerte HoekeDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Zhuang LiDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Arthur C EibergenDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Amber W SchonkDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Martijn KoehorstDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Renze BoverhofDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Rick HavingaDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Folkert KuipersDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Tamer CoskunDepartment of Diabetes/Endocrine, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.
Mariëtte R BoonDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Albert K GroenDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Patrick C N RensenDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Jimmy F P BerbéeDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Yanan WangDivision of Endocrinology, Department of Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Leiden University Medical Center · NLUniversity Medical Center Groningen · NLEli Lilly (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsBrown fat activation accelerates the uptake of cholesterol-enriched remnants by the liver and thereby lowers plasma cholesterol, consequently protecting against atherosclerosis development. Hepatic cholesterol is then converted into bile acids (BAs) that are secreted into the intestine and largely maintained within the enterohepatic circulation. We now aimed to evaluate the effects of prolonged brown fat activation combined with inhibition of intestinal BA reabsorption on plasma cholesterol metabolism and atherosclerosis development. METHODS AND

resultsAPOE*3-Leiden.CETP mice with humanized lipoprotein metabolism were treated for 9 weeks with the selective β3-adrenergic receptor (AR) agonist CL316,243 to substantially activate brown fat. Prolonged β3-AR agonism reduced faecal BA excretion (-31%), while markedly increasing plasma levels of total BAs (+258%), cholic acid-derived BAs (+295%), and chenodeoxycholic acid-derived BAs (+217%), and decreasing the expression of hepatic genes involved in BA production. In subsequent experiments, mice were additionally treated with the BA sequestrant Colesevelam to inhibit BA reabsorption. Concomitant intestinal BA sequestration increased faecal BA excretion, normalized plasma BA levels, and reduced hepatic cholesterol. Moreover, concomitant BA sequestration further reduced plasma total cholesterol (-49%) and non-high-density lipoprotein cholesterol (-56%), tended to further attenuate atherosclerotic lesion area (-54%). Concomitant BA sequestration further increased the proportion of lesion-free valves (+34%) and decreased the relative macrophage area within the lesion (-26%), thereby further increasing the plaque stability index (+44%).

conclusionBA sequestration prevents the marked accumulation of plasma BAs as induced by prolonged brown fat activation, thereby further improving cholesterol metabolism and reducing atherosclerosis development. These data suggest that combining brown fat activation with BA sequestration is a promising new therapeutic strategy to reduce hyperlipidaemia and cardiovascular diseases.

Indexed as

Adipose Tissue, BrownAdrenergic beta-3 Receptor AgonistsAnimalsAnticholesteremic AgentsApolipoprotein E3AtherosclerosisBile Acids and SaltsCholesterolCholesterol Ester Transfer ProteinsColesevelam HydrochlorideDioxolesDisease Models, AnimalEnterohepatic CirculationFecesHyperlipidemiasIntestinal AbsorptionAdrenergic beta-3 Receptor AgonistsAnticholesteremic AgentsApolipoprotein E3Bile Acids and SaltsCETP protein, humanCholesterolCholesterol Ester Transfer ProteinsColesevelam HydrochlorideDioxolesdisodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylateAtherosclerosisBile acid metabolismBrown adipose tissueCholesterol turnoverHyperlipidaemia

Identifiers

PMID31589318
PMCPMC7643538
OpenAlexW2980188004

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.