Int J Mol Sci.: auth.: W.Wahli

 2019 Oct 15;20(20). pii: E5115. doi: 10.3390/ijms20205115.

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

Chen J1,2Zhuang Y1Sng MK1,2Tan NS1,2Wahli W3,4,5.


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+ 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/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/ 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 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-/- mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD.


FSP1; Pparb/d; fatty acid β-oxidation, fatty acid synthesis and triglyceride synthesis; lipid metabolism; steatosis

PMID: 31618976