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| Status |
Public on Mar 09, 2021 |
| Title |
Hepatic miR20b promotes nonalcholic fatty liver diseases by targeting PPARα |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Nuclear receptors (NRs) play a crucial role in non-alcoholic fatty liver disease (NAFLD) and have been widely studied(Tran et al. 2018). However, the underlying mechanisms of NR regulation remain largely unclear. Here, we show that miR-20b plays a key role in modulating PPARα, a master regulator of nutrient metabolism and energy homeostasis in the pathogenesis of fatty liver(Wahli et al. 1995; Dongiovanni and Valenti 2013). Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in NAFLD patients, we revealed that miR-20b directly targets PPARα. The expression of miR-20b was remarkably upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of miR-20b dramatically increased hepatic lipid accumulation and plasma triglyceride levels. Furthermore, miR-20b significantly reduced fatty acid oxidation and mitochondrial biogenesis by directly targeting PPARα. Fenofibrate, a specific agonist of PPARα, lost its ability to ameliorate hepatic steatosis in miR-20b-introduced mice. Finally, inhibition of miR-20b dramatically increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Taken together, these results demonstrate that the novel miR-20b directly targets PPARα, plays a significant role in hepatic lipid metabolism, and presents an opportunity for the development of novel therapeutics for NAFLD.
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| Overall design |
Analysis of differential expression (DE) caused by over expression (mimic) of hsa-miR-20b
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| Contributor(s) |
Kim S, Lee Y, Jang H |
| Citation(s) |
34964438 |
| Submission date |
Mar 08, 2021 |
| Last update date |
Jan 28, 2022 |
| Contact name |
Sounkou Kim |
| E-mail(s) |
victorkim@unist.ac.kr
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| Organization name |
Ulsan National Institute of Science and Technology
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| Department |
Department of Biological Science
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| Lab |
Bioinformatics Lab
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| Street address |
110-603, 50, UNIST-gil
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| City |
Eonyang-eup, Ulju-gun |
| State/province |
Ulsan |
| ZIP/Postal code |
44919 |
| Country |
South Korea |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA707547 |
| SRA |
SRP309809 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE168484_gene_count_symbols_unique.csv.gz |
501.2 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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