The whole transcriptome effects of the PPAR? agonist fenofibrate on livers of hepatocyte humanized mice.

ABSTRACT: BACKGROUND:The role of PPAR? in gene regulation in mouse liver is well characterized. However, less is known about the role of PPAR? in human liver. The aim of the present study was to better characterize the impact of PPAR? activation on gene regulation in human liver. To that end, chimeric mice containing hepatocyte humanized livers were given an oral dose of 300 mg/kg fenofibrate daily for 4 days. Livers were collected and analyzed by hematoxilin and eosin staining, qPCR, and transcriptomics. Transcriptomics data were compared with existing datasets on PPAR? activation in normal mouse liver, human primary hepatocytes, and human precision cut liver slices. RESULTS:Of the different human liver models, the gene expression profile of hepatocyte humanized livers most closely resembled actual human liver. In the hepatocyte humanized mouse livers, the human hepatocytes exhibited excessive lipid accumulation. Fenofibrate increased the size of the mouse but not human hepatocytes, and tended to reduce steatosis in the human hepatocytes. Quantitative PCR indicated that induction of PPAR? targets by fenofibrate was less pronounced in the human hepatocytes than in the residual mouse hepatocytes. Transcriptomics analysis indicated that, after filtering, a total of 282 genes was significantly different between fenofibrate- and control-treated mice (P?

SUBMITTER: de la Rosa Rodriguez MA 

PROVIDER: S-EPMC5991453 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature