Transient Hepatic Overexpression of Insulin-Like Growth Factor 2 Induces Free Cholesterol and Lipid Droplet Formation.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsKessler, Sonja M
Van Wonterg, Elien
Vandenbroucke, Roosmarijn E
Kiemer, Alexandra K
MetadataShow full item record
AbstractAlthough 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.
CitationTransient Hepatic Overexpression of Insulin-Like Growth Factor 2 Induces Free Cholesterol and Lipid Droplet Formation. 2016, 7:147 Front Physiol
AffiliationHelmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken.
JournalFrontiers in physiology
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Elevated free cholesterol in a p62 overexpression model of non-alcoholic steatohepatitis.
- Authors: Simon Y, Kessler SM, Gemperlein K, Bohle RM, Müller R, Haybaeck J, Kiemer AK
- Issue date: 2014 Dec 21
- The IGF2 mRNA binding protein p62/IGF2BP2-2 induces fatty acid elongation as a critical feature of steatosis.
- Authors: Laggai S, Kessler SM, Boettcher S, Lebrun V, Gemperlein K, Lederer E, Leclercq IA, Mueller R, Hartmann RW, Haybaeck J, Kiemer AK
- Issue date: 2014 Jun
- Corrigendum: Transient Hepatic Overexpression of Insulin-Like Growth Factor 2 Induces Free Cholesterol and Lipid Droplet Formation.
- Authors: Kessler SM, Laggai S, Van Wonterghem E, Gemperlein K, Müller R, Haybaeck J, Vandenbroucke RE, Ogris M, Libert C, Kiemer AK
- Issue date: 2016
- Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse non-alcoholic steatohepatitis.
- Authors: Liu MX, Gao M, Li CZ, Yu CZ, Yan H, Peng C, Li Y, Li CG, Ma ZL, Zhao Y, Pu MF, Miao LL, Qi XM, Ren J
- Issue date: 2017 May
- Cholesterol Crystals in Hepatocyte Lipid Droplets Are Strongly Associated With Human Nonalcoholic Steatohepatitis.
- Authors: Ioannou GN, Landis CS, Jin GY, Haigh WG, Farrell GC, Kuver R, Lee SP, Savard C
- Issue date: 2019 Jun