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| Status |
Public on Oct 28, 2022 |
| Title |
Blockage of PPARg T166 phosphorylation enhances the inducibility of beige adipocytes and improves metabolic dysfunctions |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Beige adipocytes in mammalian white adipose tissue (WAT) can reinforce fat catabolism and energy expenditure. Promoting beige adipocyte biogenesis is a tantalizing tactic for combating obesity and its associated metabolic disorders. Here, we report that a previously unidentified phosphorylation pattern (Thr166) in the DNA-binding domain of PPARg regulates the inducibility of beige adipocytes. This unique posttranslational modification (PTM) pattern influences allosteric communication between PPARg and DNA or coactivators, which impedes the PPARg-mediated transactivation of beige cell-related gene expression in WAT. The genetic mutation mimicking T166 phosphorylation (p-T166) hinders the inducibility of beige adipocytes. In contrast, genetic or chemical intervention in this PTM pattern favors beige cell formation. Moreover, inhibition of p-T166 attenuates metabolic dysfunction in obese mice. Our results uncover a mechanism involved in beige cell fate determination. Moreover, our discoveries provide a promising strategy for guiding the development of novel PPARg agonists for the treatment of obesity and related metabolic disorders.
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| Overall design |
mRNA profiling of SVF differentiated adipocytes from PPARg WT, T166A and T166D mutant mice.
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| Contributor(s) |
Yang N, Wang Y, Shen P |
| Citation(s) |
36329235 |
| BioProject |
PRJNA665140 |
| |
| Submission date |
Sep 27, 2020 |
| Last update date |
Nov 13, 2022 |
| Contact name |
Yuxin Wang |
| E-mail(s) |
541552695@qq.com, yxwang@smail.nju.edu.cn
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| Organization name |
Nanjing University
|
| Street address |
163 Xianlin Road
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| City |
Nanjing |
| ZIP/Postal code |
210023 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| Relations |
| SRA |
SRP285062 |
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