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The whole transcriptome effects of the PPARα agonist fenofibrate on livers of hepatocyte humanized mice

Overview of attention for article published in BMC Genomics, June 2018
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Title
The whole transcriptome effects of the PPARα agonist fenofibrate on livers of hepatocyte humanized mice
Published in
BMC Genomics, June 2018
DOI 10.1186/s12864-018-4834-3
Pubmed ID
Authors

Montserrat A. de la Rosa Rodriguez, Go Sugahara, Guido J. E. J. Hooiveld, Yuji Ishida, Chise Tateno, Sander Kersten

Abstract

The role of PPARα in gene regulation in mouse liver is well characterized. However, less is known about the role of PPARα in human liver. The aim of the present study was to better characterize the impact of PPARα 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 PPARα activation in normal mouse liver, human primary hepatocytes, and human precision cut liver slices. 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 PPARα 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 < 0.01). 123 genes were significantly lower and 159 genes significantly higher in the fenofibrate-treated mice, including many established PPARα targets such as FABP1, HADHB, HADHA, VNN1, PLIN2, ACADVL and HMGCS2. According to gene set enrichment analysis, fenofibrate upregulated interferon/cytokine signaling-related pathways in hepatocyte humanized liver, but downregulated these pathways in normal mouse liver. Also, fenofibrate downregulated pathways related to DNA synthesis in hepatocyte humanized liver but not in normal mouse liver. The results support the major role of PPARα in regulating hepatic lipid metabolism, and underscore the more modest effect of PPARα activation on gene regulation in human liver compared to mouse liver. The data suggest that PPARα may have a suppressive effect on DNA synthesis in human liver, and a stimulatory effect on interferon/cytokine signalling.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 44 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 25%
Researcher 8 18%
Student > Master 4 9%
Student > Bachelor 3 7%
Student > Postgraduate 2 5%
Other 3 7%
Unknown 13 30%
Readers by discipline Count As %
Medicine and Dentistry 7 16%
Agricultural and Biological Sciences 5 11%
Biochemistry, Genetics and Molecular Biology 4 9%
Pharmacology, Toxicology and Pharmaceutical Science 4 9%
Nursing and Health Professions 1 2%
Other 6 14%
Unknown 17 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 June 2018.
All research outputs
#15,535,385
of 23,088,369 outputs
Outputs from BMC Genomics
#6,724
of 10,705 outputs
Outputs of similar age
#209,569
of 329,367 outputs
Outputs of similar age from BMC Genomics
#150
of 250 outputs
Altmetric has tracked 23,088,369 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 10,705 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,367 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 250 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.