The Potential of the FSP1cre-Pparb/d<sup>-</sup><sup>/</sup><sup>-</sup> Mouse Model for Studying Juvenile NAFLD.

Details

Serval ID
serval:BIB_9AE31044F6EF
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
The Potential of the FSP1cre-Pparb/d<sup>-</sup><sup>/</sup><sup>-</sup> Mouse Model for Studying Juvenile NAFLD.
Journal
International journal of molecular sciences
Author(s)
Chen J., Zhuang Y., Sng M.K., Tan N.S., Wahli W.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
15/10/2019
Peer-reviewed
Oui
Volume
20
Number
20
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it is unknown whether the resident CD68 <sup>+</sup> or bone marrow-derived CD11b <sup>+</sup> Kupffer cells are involved. Characterization of the FSP1cre-Pparb/d <sup>-</sup> <sup>/</sup> <sup>-</sup> mouse liver revealed that FSP1 is expressed in CD11b <sup>+</sup> Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population, Pparb/d deletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipid content was present in postnatal day 2 (P2) FSP1cre-Pparb/d <sup>-</sup> <sup>/</sup> <sup>-</sup> livers, which diminished after weaning. Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d <sup>-/-</sup> livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fatty acid β-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supported by western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d <sup>-/-</sup> mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD.
Keywords
Animals, Biomarkers, Disease Models, Animal, Fatty Acids/metabolism, Hepatocytes/metabolism, Intracellular Space/metabolism, Kupffer Cells/metabolism, Lipid Metabolism, Mice, Mice, Transgenic, Models, Biological, Non-alcoholic Fatty Liver Disease/etiology, Non-alcoholic Fatty Liver Disease/metabolism, Oxidation-Reduction, PPAR-beta/genetics, PPAR-beta/metabolism, S100 Calcium-Binding Protein A4/genetics, S100 Calcium-Binding Protein A4/metabolism, FSP1, Pparb/d, fatty acid β-oxidation, fatty acid synthesis and triglyceride synthesis, lipid metabolism, steatosis
Pubmed
Web of science
Open Access
Yes
Create date
21/10/2019 16:55
Last modification date
28/05/2021 6:36
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