Evidence map›Paper›PMID 32698042›Full record

ArticleCellular and molecular gastroenterology and hepatology2021

Impaired Hepatic Vitamin A Metabolism in NAFLD Mice Leading to Vitamin A Accumulation in Hepatocytes.

Ali Saeed, Paulina Bartuzi, Janette Heegsma, Daphne Dekker, Niels Kloosterhuis, Alain de Bruin, Johan W Jonker, Bart van de Sluis, Klaas Nico Faber

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

Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 20% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Sex and Age but Not Body Mass Index (BMI) Predict Serum Retinol Binding Protein 4 (RBP4) and Transthyretin (TTR) Concentrations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  4. The Role of Lipid Metabolic Reprogramming in the Hibernation of Chipmunks.Animals : an open access journal from MDPI · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Retinoic Acid Signaling in Fatty Liver Disease.Liver research (Beijing, China) · 2023
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 3 countries.

Ali SaeedDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan. Electronic address: a.saeed@umcg.nl.
Paulina BartuziSection of Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Janette HeegsmaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Laboratory Medicine, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Daphne DekkerSection of Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Niels KloosterhuisSection of Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Alain de BruinSection of Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Johan W JonkerSection of Molecular Metabolism and Nutrition, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Bart van de SluisSection of Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Klaas Nico FaberDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Laboratory Medicine, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: k.n.faber@umcg.nl.
University Medical Center Groningen · NLBahauddin Zakariya University · PK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsSystemic retinol (vitamin A) homeostasis is controlled by the liver, involving close collaboration between hepatocytes and hepatic stellate cells (HSCs). Genetic variants in retinol metabolism (PNPLA3 and HSD17B13) are associated with non-alcoholic fatty liver disease (NAFLD) and disease progression. Still, little mechanistic details are known about hepatic vitamin A metabolism in NAFLD, which may affect carbohydrate and lipid metabolism, inflammation, oxidative stress and the development of fibrosis and cancer, e.g. all risk factors of NAFLD.

methodsHere, we analyzed vitamin A metabolism in 2 mouse models of NAFLD; mice fed a high-fat, high-cholesterol (HFC) diet and Leptin

resultsHepatic retinol and retinol binding protein 4 (RBP4) levels were significantly reduced in both mouse models of NAFLD. In contrast, hepatic retinyl palmitate levels (the vitamin A storage form) were significantly elevated in these mice. Transcriptome analysis revealed a hyperdynamic state of hepatic vitamin A metabolism, with enhanced retinol storage and metabolism (upregulated Lrat, Dgat1, Pnpla3, Raldh's and RAR/RXR-target genes) in fatty livers, in conjunction with induced hepatic inflammation (upregulated Cd68, Tnfα, Nos2, Il1β, Il-6) and fibrosis (upregulated Col1a1, Acta2, Tgfβ, Timp1). Autofluorescence analyses revealed prominent vitamin A accumulation in hepatocytes rather than HSC in HFC-fed mice. Palmitic acid exposure increased Lrat mRNA levels in primary rat hepatocytes and promoted retinyl palmitate accumulation when co-treated with retinol, which was not detected for similarly-treated primary rat HSCs.

conclusionNAFLD leads to cell type-specific rearrangements in retinol metabolism leading to vitamin A accumulation in hepatocytes. This may promote disease progression and/or affect therapeutic approaches targeting nuclear receptors.

Indexed as

17-Hydroxysteroid DehydrogenasesAcyltransferasesAnimalsDiet, High-FatDisease Models, AnimalDisease ProgressionFemaleHepatic Stellate CellsHepatocytesHumansLeptinLipid MetabolismLiverMaleMiceMice, Transgenic17beta-hydroxysteroid dehydrogenase type 13, mouse17-Hydroxysteroid DehydrogenasesAcyltransferasesLeptinPhospholipases A2, Calcium-IndependentPNPLA3 protein, mouseRbp4 protein, mouseRetinol-Binding Proteins, PlasmaVitamin AAutofluorescenceFatty Liver DiseaseVitamin A

Identifiers

PMID32698042
PMCPMC7768561
OpenAlexW2902467986

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.