Bmp8b-KO Mouse

Bmp8b, or Bone morphogenetic protein 8B, is a protein-coding gene that belongs to the transforming growth factor beta (TGFβ)-BMP superfamily. It plays a crucial role in regulating energy homeostasis, especially in the thermogenesis of brown adipose tissue (BAT) and the browning of white adipose tissue (WAT) [1,2,4,6,7]. Bmp8b functions through signaling pathways such as SMAD2/3, NF-κB, and p38MAPK/CREB, and is also associated with the MAPK signaling pathway in certain contexts [1,3].

In Bmp8b(-/-) mice, impaired thermogenesis and reduced metabolic rate were observed, leading to weight gain despite hypophagia, indicating its importance in regulating energy balance [4]. In the context of non-alcoholic steatohepatitis (NASH), the absence of BMP8B in vivo prevented hepatic stellate cell (HSC) activation, reduced inflammation, and limited NASH progression, suggesting its role in promoting NASH [5]. Obesity-induced resistance to the central actions of BMP8B was associated with decreased BMP receptors signaling and reduced expression of BBS1 in the ventromedial nucleus of the hypothalamus in HFD-fed rats and genetically modified mice, uncovering a new mechanism of central resistance to hormonal action in obesity [7].

In conclusion, Bmp8b is a key regulator of energy balance, influencing thermogenesis in adipose tissues. Its role in disease conditions such as NASH and obesity-related resistance has been illuminated through gene knockout mouse models. These findings suggest Bmp8b could be a potential therapeutic target for metabolic diseases.

References:

1. Zhong, Shenjie, Du, Xueqing, Gao, Jing, Ji, Guangdong, Liu, Zhenhui. 2023. BMP8B Activates Both SMAD2/3 and NF-κB Signals to Inhibit the Differentiation of 3T3-L1 Preadipocytes into Mature Adipocytes. In Nutrients, 16, . doi:10.3390/nu16010064. https://pubmed.ncbi.nlm.nih.gov/38201894/

2. Liu, Jingxin, Wang, Yitao, Lin, Ligen. 2018. Small molecules for fat combustion: targeting obesity. In Acta pharmaceutica Sinica. B, 9, 220-236. doi:10.1016/j.apsb.2018.09.007. https://pubmed.ncbi.nlm.nih.gov/30976490/

3. Wang, Meng, Zhong, Liang, Zhang, Hongyan, Yu, Lihua, Liu, Beizhong. 2024. p200CUX1-regulated BMP8B inhibits the progression of acute myeloid leukemia via the MAPK signaling pathway. In Medical oncology (Northwood, London, England), 41, 166. doi:10.1007/s12032-024-02398-2. https://pubmed.ncbi.nlm.nih.gov/38819709/

4. Whittle, Andrew J, Carobbio, Stefania, Martins, Luís, López, Miguel, Vidal-Puig, Antonio. . BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. In Cell, 149, 871-85. doi:10.1016/j.cell.2012.02.066. https://pubmed.ncbi.nlm.nih.gov/22579288/

5. Vacca, Michele, Leslie, Jack, Virtue, Samuel, Oakley, Fiona, Vidal-Puig, Antonio. 2020. Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis. In Nature metabolism, 2, 514-531. doi:10.1038/s42255-020-0214-9. https://pubmed.ncbi.nlm.nih.gov/32694734/

6. Pellegrinelli, Vanessa, Peirce, Vivian J, Howard, Laura, Davies, Alun M, Vidal-Puig, Antonio. 2018. Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue. In Nature communications, 9, 4974. doi:10.1038/s41467-018-07453-x. https://pubmed.ncbi.nlm.nih.gov/30478315/

7. Rial-Pensado, Eva, Freire-Agulleiro, Oscar, Ríos, Marcos, Rahmouni, Kamal, López, Miguel. 2022. Obesity induces resistance to central action of BMP8B through a mechanism involving the BBSome. In Molecular metabolism, 59, 101465. doi:10.1016/j.molmet.2022.101465. https://pubmed.ncbi.nlm.nih.gov/35218946/