BMP8B Activates Both SMAD2/3 and NF-κB Signals to Inhibit the Differentiation of 3T3-L1 Preadipocytes into Mature Adipocytes

Shenjie Zhong; Xueqing Du; Jing Gao; Guangdong Ji; Zhenhui Liu

doi:10.3390/nu16010064

BMP8B Activates Both SMAD2/3 and NF-κB Signals to Inhibit the Differentiation of 3T3-L1 Preadipocytes into Mature Adipocytes

Nutrients. 2023 Dec 25;16(1):64. doi: 10.3390/nu16010064.

Authors

Shenjie Zhong¹, Xueqing Du¹, Jing Gao¹, Guangdong Ji^{1

2}, Zhenhui Liu^{1

2}

Affiliations

¹ College of Marine Life Sciences, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.
² Laoshan Laboratory, Qingdao 266237, China.

Abstract

Bone morphogenetic protein 8B (BMP8B) has been found to regulate the thermogenesis of brown adipose tissue (BAT) and the browning process of white adipose tissue (WAT). However, there is no available information regarding the role of BMP8B in the process of adipocyte differentiation. Here, we showed that BMP8B down-regulates transcriptional regulators PPARγ and C/EBPα, thereby impeding the differentiation of 3T3-L1 preadipocytes into fully mature adipocytes. BMP8B increased the phosphorylation levels of SMAD2/3, and TP0427736 HCl (SMAD2/3 inhibitor) significantly reduced the ability of BMP8B to inhibit adipocyte differentiation, suggesting that BMP8B repressed adipocyte differentiation through the SMAD2/3 pathway. Moreover, the knockdown of BMP I receptor ALK4 significantly reduced the inhibitory effect of BMP8B on adipogenesis, indicating that BMP8B triggers SMAD2/3 signaling to suppress adipogenesis via ALK4. In addition, BMP8B activated the NF-κB signal, which has been demonstrated to impede PPARγ expression. Collectively, our data demonstrated that BMP8B activates both SMAD2/3 and NF-κB signals to inhibit adipocyte differentiation. We provide previously unidentified insight into BMP8B-mediated adipogenesis.

Keywords: 3T3-L1; BMP8B; NF-κB; SMAD2/3; adipocyte differentiation.

MeSH terms

3T3-L1 Cells
Adipocytes
Animals
Bone Morphogenetic Proteins
Mice
NF-kappa B*
PPAR gamma* / genetics

Substances

NF-kappa B
PPAR gamma
Bone Morphogenetic Proteins

Grants and funding

The research presented in this paper was funded by Science & Technology Innovation Project of Laoshan Laboratory (grant number: LSKJ202203204), National Key Research and Development Project of the Ministry of Science and Technology (grant number: 2023YFE0199500), and Shandong Provincial Natural Science Foundation (grant number: ZR2022MC032).