Evidence map›Paper›PMID 36432620›Full record

ArticleNutrients2022

A Systems Analysis of Phenotype Heterogeneity in APOE*3Leiden.CETP Mice Induced by Long-Term High-Fat High-Cholesterol Diet Feeding.

Yared Paalvast, Enchen Zhou, Yvonne J W Rozendaal, Yanan Wang, Albert Gerding, Theo H van Dijk, Jan Freark de Boer, Patrick C N Rensen, Ko Willems van Dijk, Jan A Kuivenhoven and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
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

13 authors at 4 institutions in 1 country.

Yared PaalvastDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.ORCID 0000-0003-1648-9851
Enchen ZhouDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Yvonne J W RozendaalDepartment of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.ORCID 0000-0003-1812-7694
Yanan WangDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.ORCID 0000-0002-0327-0458
Albert GerdingDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
Theo H van DijkDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
Jan Freark de BoerDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.ORCID 0000-0001-6759-3291
Patrick C N RensenDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.ORCID 0000-0002-8455-4988
Ko Willems van DijkEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.ORCID 0000-0002-2172-7394
Jan A KuivenhovenDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
Barbara M BakkerDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
Natal A W van RielDepartment of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.ORCID 0000-0001-9375-4730
Albert K GroenDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
University Medical Center Groningen · NLLeiden University Medical Center · NLAmsterdam University Medical Centers · NLEindhoven University of Technology · NL

Funding

CVON 2009T038CVON 2015T068European Union FP7-603091European Union FP7- HEALTH n°305707
6 · The paper itself

Abstract

Within the human population, considerable variability exists between individuals in their susceptibility to develop obesity and dyslipidemia. In humans, this is thought to be caused by both genetic and environmental variation. APOE*3-Leiden.CETP mice, as part of an inbred mouse model in which mice develop the metabolic syndrome upon being fed a high-fat high-cholesterol diet, show large inter-individual variation in the parameters of the metabolic syndrome, despite a lack of genetic and environmental variation. In the present study, we set out to resolve what mechanisms could underlie this variation. We used measurements of glucose and lipid metabolism from a six-month longitudinal study on the development of the metabolic syndrome. Mice were classified as mice with either high plasma triglyceride (responders) or low plasma triglyceride (non-responders) at the baseline. Subsequently, we fitted the data to a dynamic computational model of whole-body glucose and lipid metabolism (MINGLeD) by making use of a hybrid modelling method called Adaptations in Parameter Trajectories (ADAPT). ADAPT integrates longitudinal data, and predicts how the parameters of the model must change through time in order to comply with the data and model constraints. To explain the phenotypic variation in plasma triglycerides, the ADAPT analysis suggested a decreased cholesterol absorption, higher energy expenditure and increased fecal fatty acid excretion in non-responders. While decreased cholesterol absorption and higher energy expenditure could not be confirmed, the experimental validation demonstrated that the non-responders were indeed characterized by increased fecal fatty acid excretion. Furthermore, the amount of fatty acids excreted strongly correlated with bile acid excretion, in particular deoxycholate. Since bile acids play an important role in the solubilization of lipids in the intestine, these results suggest that variation in bile acid homeostasis may in part drive the phenotypic variation in the APOE*3-Leiden.CETP mice.

Indexed as

Apolipoprotein E3Cholesterol Ester Transfer ProteinsDiet, High-FatMetabolic SyndromeAnimalsBile Acids and SaltsCholesterolFatty AcidsGlucoseLiverLongitudinal StudiesMicePhenotypeSystems AnalysisTriglyceridesApolipoprotein E3apolipoprotein E3 (Leidein)Bile Acids and SaltsCholesterolCholesterol Ester Transfer ProteinsFatty AcidsGlucoseTriglyceridesAPOE3bile acidCETPcholesterolcomputational modelingenergy expendituremetabolic syndrometriglycerides

Identifiers

PMID36432620
PMCPMC9698005
OpenAlexW4309717545

What OpenQuestion holds

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LicenceCC BY
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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.