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| Status |
Public on Mar 24, 2021 |
| Title |
Brd4 modulates diet-induced obesity via PPARĪ³-dependent Gdf3 expression in adipose tissue macrophages |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Macrophage-mediated inflammatory response has been implicated in the pathogenesis of obesity and insulin resistance. Brd4 has emerged as a key regulator in the innate immune response. However, the role of Brd4 in obesity-associated inflammation and insulin resistance remains uncharacterized. Here, we demonstrated that myeloid-lineage specific Brd4 knockout (Brd4-CKO) mice were protected from high-fat-diet (HFD)-induced obesity with less fat accumulation, higher energy expenditure, and increased lipolysis in adipose tissue. Brd4-CKO mice also displayed reduced local and systemic inflammation with improved insulin sensitivity upon HFD. RNA-sequencing of adipose tissue macrophages (ATMs) from HFD-fed wide-type and Brd4-CKO mice revealed that expression of antilipolytic factor Gdf3 was significantly decreased in ATMs of Brd4-CKO mice. We also found that Brd4 bound to the promoter and enhancers of Gdf3 to facilitate PPARĪ³-dependent Gdf3 expression in macrophages. Furthermore, Brd4-mediated expression of Gdf3 acted as a paracrine signal targeting adipocytes to suppress the expression of lipases and the associated lipolysis in cultured cells and mice. Controlling the expression of Gdf3 in ATMs could be one of the mechanisms by which Brd4 modulates lipid metabolism and diet-induced obesity. This study suggests that Brd4 could be a potential therapeutic target for obesity and insulin resistance.
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| Overall design |
Gene expression of adipose tisssue macrophages from Brd4-CKO mice was compared to wile type mice.
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| Contributor(s) |
Hu X, Dong X, Li G, Chen J, He X, Sun H, Kim D, Kemper J, Chen L |
| Citation(s) |
33830083 |
| BioProject |
PRJNA715815 |
| Submission date |
Mar 23, 2021 |
| Last update date |
Jun 23, 2021 |
| Contact name |
guo Li |
| E-mail(s) |
guo_li@fjmu.edu.cn
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| Organization name |
Fujian medical university
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| Street address |
shangjie road
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| City |
fuzhou city |
| State/province |
fujian province |
| ZIP/Postal code |
350122 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| SRA |
SRP311439 |
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