The potential of the FSP1cre-Pparb/d−/− Mouse model for studying juvenile NAFLD

Jiapeng Chen (1, 2) , Yan Zhuang (1) , Ming Keat Sng (1, 2) , Nguan Soon Tan (1, 2) , Walter Wahli (3, 1, 4)

1 Lee Kong Chian School of Medicine
2 School of Biological Sciences
3 ToxAlim - ToxAlim
4 CIG - Center for Integrative Genomics - Institute of Bioinformatics, Génopode

Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholicsteatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis andhepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fatdiet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it isunknown whether the resident CD68+or bone marrow-derived CD11b+Kupffer cells are involved.Characterization of the FSP1cre-Pparb/d−/−mouse liver revealed that FSP1 is expressed in CD11b+Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population,Pparb/ddeletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipidcontent was present in postnatal day 2 (P2) FSP1cre-Pparb/d−/−livers, which diminished after weaning.Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d−/−livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fattyacidβ-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supportedby western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d−/−mice, which accumulate lipids in their liver in early life, may represent a useful animal model tostudy juvenile NAFLD.

Mots clés: Pparb/d; FSP1; lipid metabolism; steatosis; fatty acidβ-oxidation; fatty acid synthesis; triglyceride synthesis

Domaines: Toxicologie

Jiapeng Chen, Yan Zhuang, Ming Keat Sng, Nguan Soon Tan, Walter Wahli. The potential of the FSP1cre-Pparb/d−/− Mouse model for studying juvenile NAFLD. International Journal of Molecular Sciences, 2019, 20 (20), pp.5115. ⟨10.3390/ijms20205115⟩. ⟨hal-02618392⟩