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| Status |
Public on Jan 21, 2020 |
| Title |
miR-26 suppresses adipocyte progenitor differentiation and fat production by targeting Fbxl19 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Purpose: Fat storage in adult mammals is a highly regulated process that involves the mobilization of adipocyte progenitor cells (APCs) that differentiate to produce new adipocytes. Here we report an unexpected role for the broadly conserved miR-26 family of microRNAs (miR-26a-1, miR-26a-2, and miR-26b) as key regulators of APC differentiation. Global loss of miR-26 resulted in a dramatic expansion of adipose tissue in adult mice fed normal chow. Conversely, transgenic overexpression of miR-26a protected mice from high fat diet-induced obesity. These effects were attributable to a cell-autonomous function of miR-26 as a potent inhibitor of APC differentiation. miR-26 blocks adipogenesis, at least in part, by repressing expression of Fbxl19, a conserved miR-26 target without a previously known role in adipocyte biology that encodes a component of SCF-type E3 ubiquitin ligase complexes. These findings have therefore revealed a new pathway that plays a critical role in regulating adipose tissue formation in vivo and suggest new potential therapeutic targets for obesity and related disorders.
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| Overall design |
Method: miR-26 targets in adipocyte progenitor cell differentiation were identified by RNA seq analysis of primary stromal vascular fraction cultured in vitro from i) wild-type C57BL/6 and miR-TKO mice, and ii) M2rtTA; eGFP.miR-26a mice with or without 1 mg/mL dox treatment for 4 days.
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| |
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| Contributor(s) |
Acharya A, Zhang H, Mendell JT |
| Citation(s) |
31488578 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R35 CA197311 |
The intersection of RNA biology and tumor biology |
UT SOUTHWESTERN MEDICAL CENTER |
Joshua T Mendell |
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| |
| Submission date |
Jul 23, 2019 |
| Last update date |
Apr 21, 2020 |
| Contact name |
Joshua Mendell |
| E-mail(s) |
joshua.mendell@utsouthwestern.edu
|
| Organization name |
UT Southwestern Medical Center
|
| Department |
Molecular Biology
|
| Street address |
6000 Harry Hines Blvd., NA6.200A
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9148 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA556241 |
| SRA |
SRP216065 |
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