PUBLICATION
Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation
- Authors
- Zhong, S., Chen, L., Li, X., Wang, X., Ji, G., Sun, C., Liu, Z.
- ID
- ZDB-PUB-230810-57
- Date
- 2023
- Source
- Communications biology 6: 824824 (Journal)
- Registered Authors
- Liu, Zhenhui
- Keywords
- none
- MeSH Terms
-
- 3T3-L1 Cells
- Adipocytes*/metabolism
- Animals
- Bone Morphogenetic Proteins*/genetics
- Cell Differentiation/genetics
- Fatty Acids/metabolism
- Lipid Metabolism*/genetics
- Mice
- NF-kappa B/metabolism
- Obesity*/metabolism
- PPAR gamma/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- PubMed
- 37553521 Full text @ Commun Biol
Citation
Zhong, S., Chen, L., Li, X., Wang, X., Ji, G., Sun, C., Liu, Z. (2023) Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation. Communications biology. 6:824824.
Abstract
The role of bone morphogenetic proteins (BMPs) in regulating adipose has recently become a field of interest. However, the underlying mechanism of this effect has not been elucidated. Here we show that the anti-fat effect of Bmp8a is mediated by promoting fatty acid oxidation and inhibiting adipocyte differentiation. Knocking out the bmp8a gene in zebrafish results in weight gain, fatty liver, and increased fat production. The bmp8a-/- zebrafish exhibits decreased phosphorylation levels of AMPK and ACC in the liver and adipose tissues, indicating reduced fatty acid oxidation. Also, Bmp8a inhibits the differentiation of 3T3-L1 preadipocytes into mature adipocytes by activating the Smad2/3 signaling pathway, in which Smad2/3 binds to the central adipogenic factor PPARγ promoter to inhibit its transcription. In addition, lentivirus-mediated overexpression of Bmp8a in 3T3-L1 cells significantly increases NOD-like receptor, TNF, and NF-κB signaling pathways. Furthermore, NF-κB interacts with PPARγ, blocking PPARγ's activation of its target gene Fabp4, thereby inhibiting adipocyte differentiation. These data bring a signal bridge between immune regulation and adipocyte differentiation. Collectively, our findings indicate that Bmp8a plays a critical role in regulating lipid metabolism and adipogenesis, potentially providing a therapeutic approach for obesity and its comorbidities.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping