Evidence map›Paper›PMID 27199763›Full record

ArticleFrontiers in physiology2016

Transient Hepatic Overexpression of Insulin-Like Growth Factor 2 Induces Free Cholesterol and Lipid Droplet Formation.

Sonja M Kessler, Stephan Laggai, Elien Van Wonterg, Katja Gemperlein, Rolf Müller, Johannes Haybaeck, Roosmarijn E Vandenbroucke, Manfred Ogris, Claude Libert, Alexandra K Kiemer

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Frontiers in physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

21 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Activation of Cx43 Hemichannels Induces the Generation of CaInternational journal of molecular sciences · 2021
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  11. Long noncoding RNA H19 - a new player in the pathogenesis of liver diseases.Translational research : the journal of laboratory and clinical medicine · 2021
    Review
  12. Article
  13. Association of Genetic Variants inFrontiers in endocrinology · 2021
    Article
  14. Review
  15. Article
  16. Frontiers in medicine · 2019
    Article
  17. Article
  18. Insulin-Like Growth Factor (IGF) System in Liver Diseases.International journal of molecular sciences · 2018
    Review
  19. Article
  20. The long non-coding RNACell stress · 2017
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

Sonja M KesslerDepartment of Pharmacy, Pharmaceutical Biology, Saarland University Saarbrücken, Germany.
Stephan LaggaiDepartment of Pharmacy, Pharmaceutical Biology, Saarland University Saarbrücken, Germany.
Elien Van WontergInflammation Research Center, VIBGhent, Belgium; Department of Biomedical Molecular Biology, Ghent UniversityGhent, Belgium.
Katja GemperleinDepartment of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University Saarbrücken, Germany.
Rolf MüllerDepartment of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University Saarbrücken, Germany.
Johannes HaybaeckInstitute of Pathology, Medical University of Graz Graz, Austria.
Roosmarijn E VandenbrouckeInflammation Research Center, VIBGhent, Belgium; Department of Biomedical Molecular Biology, Ghent UniversityGhent, Belgium.
Manfred OgrisDepartment of Pharmaceutical Chemistry, University of Vienna Vienna, Austria.
Claude LibertInflammation Research Center, VIBGhent, Belgium; Department of Biomedical Molecular Biology, Ghent UniversityGhent, Belgium.
Alexandra K KiemerDepartment of Pharmacy, Pharmaceutical Biology, Saarland University Saarbrücken, Germany.
Saarland University · DEGhent University · BEMedical University of Graz · ATUniversity of Vienna · ATVIB-UGent Center for Inflammation Research · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although insulin-like growth factor 2 (IGF2) has been reported to be overexpressed in steatosis and steatohepatitis, a causal role of IGF2 in steatosis development remains elusive. Aim of our study was to decipher the role of IGF2 in steatosis development. Hydrodynamic gene delivery of an Igf2 plasmid used for transient Igf2 overexpression employing codon-optimized plasmid DNA resulted in a strong induction of hepatic Igf2 expression. The exogenously delivered Igf2 had no influence on endogenous Igf2 expression. The downstream kinase AKT was activated in Igf2 animals. Decreased ALT levels mirrored the cytoprotective effect of IGF2. Serum cholesterol was increased and sulfo-phospho-vanillin colorimetric assay confirmed lipid accumulation in Igf2-livers while no signs of inflammation were observed. Interestingly, hepatic cholesterol and phospholipids, determined by thin layer chromatography, and free cholesterol by filipin staining, were specifically increased. Lipid droplet (LD) size was not changed, but their number was significantly elevated. Furthermore, free cholesterol, which can be stored in LDs and has been reported to be critical for steatosis progression, was elevated in Igf2 overexpressing mice. Accordingly, Hmgcr/HmgCoAR was upregulated. To have a closer look at de novo lipid synthesis we investigated expression of the lipogenic transcription factor SREBF1 and its target genes. SREBF1 was induced and also SREBF1 target genes were slightly upregulated. Interestingly, the expression of Cpt1a, which is responsible for mitochondrial fatty acid oxidation, was induced. Hepatic IGF2 expression induces a fatty liver, characterized by increased cholesterol and phospholipids leading to accumulation of LDs. We therefore suggest a causal role for IGF2 in hepatic lipid accumulation.

Indexed as

fatty liverhydrodynamic gene deliveryinsulin-like growth factor 2 (IGF2)lipid dropletsNASH

Identifiers

PMID27199763
PMCPMC4843762
OpenAlexW2344205337

What OpenQuestion holds

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Registered trials

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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.