| First Author | Chen J | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 20 |
| Issue | 20 | PubMed ID | 31618976 |
| Mgi Jnum | J:290335 | Mgi Id | MGI:6435929 |
| Doi | 10.3390/ijms20205115 | Citation | Chen J, et al. (2019) The Potential of the FSP1cre-Pparb/d(-)(/)(-) Mouse Model for Studying Juvenile NAFLD. Int J Mol Sci 20(20):5115 |
| abstractText | 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 beta-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. |
