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Attention Score in Context
| Title |
The impact of PPARα activation on whole genome gene expression in human precision cut liver slices
|
|---|---|
| Published in |
BMC Genomics, October 2015
|
| DOI | 10.1186/s12864-015-1969-3 |
| Pubmed ID | |
| Authors |
Aafke W.F. Janssen, Bark Betzel, Geert Stoopen, Frits J. Berends, Ignace M. Janssen, Ad A. Peijnenburg, Sander Kersten |
| Abstract |
Studies in mice have shown that PPARα is an important regulator of lipid metabolism in liver and key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPARα in human liver. Here we set out to study the function of PPARα in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPARα agonist Wy14643. Quantitative PCR indicated that PPARα is well expressed in human liver and human liver slices and that the classical PPARα targets PLIN2, VLDLR, ANGPTL4, CPT1A and PDK4 are robustly induced by PPARα activation. Transcriptomics analysis indicated that 617 genes were upregulated and 665 genes were downregulated by PPARα activation (q value < 0.05). Many genes induced by PPARα activation were involved in lipid metabolism (ACSL5, AGPAT9, FADS1, SLC27A4), xenobiotic metabolism (POR, ABCC2, CYP3A5) or the unfolded protein response, whereas most of the downregulated genes were involved in immune-related pathways. Among the most highly repressed genes upon PPARα activation were several chemokines (e.g. CXCL9-11, CCL8, CX3CL1, CXCL6), interferon γ-induced genes (e.g. IFITM1, IFIT1, IFIT2, IFIT3) and numerous other immune-related genes (e.g. TLR3, NOS2, and LCN2). Comparative analysis of gene regulation by Wy14643 between human liver slices and primary human hepatocytes showed that down-regulation of gene expression by PPARα is much better captured by liver slices as compared to primary hepatocytes. In particular, PPARα activation markedly suppressed immunity/inflammation-related genes in human liver slices but not in primary hepatocytes. Finally, several putative new target genes of PPARα were identified that were commonly induced by PPARα activation in the two human liver model systems, including TSKU, RHOF, CA12 and VSIG10L. Our paper demonstrates the suitability and superiority of human liver slices over primary hepatocytes for studying the functional role of PPARα in human liver. Our data underscore the major role of PPARα in regulation of hepatic lipid and xenobiotic metabolism in human liver and reveal a marked immuno-suppressive/anti-inflammatory effect of PPARα in human liver slices that may be therapeutically relevant for non-alcoholic fatty liver disease. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 14% |
| Netherlands | 1 | 14% |
| Unknown | 5 | 71% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 86% |
| Practitioners (doctors, other healthcare professionals) | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 72 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 18 | 25% |
| Researcher | 11 | 15% |
| Student > Master | 8 | 11% |
| Student > Bachelor | 7 | 10% |
| Student > Postgraduate | 6 | 8% |
| Other | 13 | 18% |
| Unknown | 9 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 20 | 28% |
| Medicine and Dentistry | 14 | 19% |
| Pharmacology, Toxicology and Pharmaceutical Science | 9 | 13% |
| Agricultural and Biological Sciences | 8 | 11% |
| Unspecified | 3 | 4% |
| Other | 7 | 10% |
| Unknown | 11 | 15% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 23 June 2016.
All research outputs
#7,223,325
of 22,829,683 outputs
Outputs from BMC Genomics
#3,428
of 10,655 outputs
Outputs of similar age
#89,629
of 278,190 outputs
Outputs of similar age from BMC Genomics
#132
of 361 outputs
Altmetric has tracked 22,829,683 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 10,655 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 66% of its peers.
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 278,190 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 361 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.