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

Overview of attention for article published in Frontiers in Physiology, April 2016
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Title
Transient Hepatic Overexpression of Insulin-Like Growth Factor 2 Induces Free Cholesterol and Lipid Droplet Formation
Published in
Frontiers in Physiology, April 2016
DOI 10.3389/fphys.2016.00147
Pubmed ID
Authors

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

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Denmark 1 2%
Unknown 40 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 20%
Student > Ph. D. Student 6 15%
Student > Bachelor 5 12%
Student > Doctoral Student 4 10%
Student > Master 4 10%
Other 4 10%
Unknown 10 24%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 8 20%
Biochemistry, Genetics and Molecular Biology 7 17%
Medicine and Dentistry 6 15%
Agricultural and Biological Sciences 6 15%
Unspecified 1 2%
Other 3 7%
Unknown 10 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 June 2016.
All research outputs
#20,333,181
of 22,877,793 outputs
Outputs from Frontiers in Physiology
#9,417
of 13,671 outputs
Outputs of similar age
#252,950
of 298,682 outputs
Outputs of similar age from Frontiers in Physiology
#93
of 131 outputs
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So far Altmetric has tracked 13,671 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 131 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.