Adrb3, also known as β3-adrenergic receptor, is predominantly expressed in brown adipose tissue (BAT). It activates BAT and is involved in metabolic health. It plays a role in the adrenergic system, which is crucial for energy metabolism [1,2,4,6].

In a study on brown adipocyte-specific ADRB3 knockout (BKO) mice, BKO markedly accelerated cardiac hypertrophy and fibrosis compared with control mice after Ang II infusion, indicating that ADRB3 activation-mediated BAT function has a role in protecting against cardiac remodeling by suppressing exosomal iNOS [1]. In breast cancer, ADRB3-/-PyMT mice showed impairment of mammary tumorigenesis and reduction in pulmonary metastasis as ADRB3 promotes metastasis by inducing mobilization and inhibiting differentiation of both breast cancer cells and myeloid-derived suppressor cells (MDSCs) [3]. In non-small cell lung carcinoma, genetic and pharmacologic inhibition of ADRB3 reversed tumor growth and inflammation in mouse models [5].

In conclusion, Adrb3 is essential for metabolic health and plays a significant role in cardiac protection, cancer metastasis, and tumor growth. The use of gene knockout mouse models has revealed its functions in these biological processes and disease conditions, providing valuable insights into potential therapeutic targets for related diseases.

References:

1. Lin, Jing-Rong, Ding, Li-Li-Qiang, Xu, Lian, Ruan, Cheng-Chao, Gao, Ping-Jin. 2022. Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS. In Circulation research, 131, 133-147. doi:10.1161/CIRCRESAHA.121.320470. https://pubmed.ncbi.nlm.nih.gov/35652349/

2. Xie, Chenyao, Hua, Wenxi, Zhao, Yuening, Yang, Xiaoqin, Xu, Xiaojing. . The ADRB3 rs4994 polymorphism increases risk of childhood and adolescent overweight/obesity for East Asia's population: an evidence-based meta-analysis. In Adipocyte, 9, 77-86. doi:10.1080/21623945.2020.1722549. https://pubmed.ncbi.nlm.nih.gov/32008426/

3. Zhou, Zhiling, Zhan, Jiaxin, Luo, Qiong, Lin, Shuguang, Zheng, Meng. 2022. ADRB3 induces mobilization and inhibits differentiation of both breast cancer cells and myeloid-derived suppressor cells. In Cell death & disease, 13, 141. doi:10.1038/s41419-022-04603-4. https://pubmed.ncbi.nlm.nih.gov/35145073/

4. Kurokawa, N, Young, E H, Oka, Y, Sandhu, M S, Loos, R J F. 2008. The ADRB3 Trp64Arg variant and BMI: a meta-analysis of 44 833 individuals. In International journal of obesity (2005), 32, 1240-9. doi:10.1038/ijo.2008.90. https://pubmed.ncbi.nlm.nih.gov/18574485/

5. Zheng, Meng, Zhou, Zhiling, Tian, Xiangting, Liang, Haidan, Lin, Shuguang. 2020. ADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non-small cell lung carcinoma. In Cancer immunology, immunotherapy : CII, 69, 2345-2355. doi:10.1007/s00262-020-02627-3. https://pubmed.ncbi.nlm.nih.gov/32514619/

6. Luo, Zhi, Zhang, Ting, Wang, Shengping, Ye, Qiutang, Cao, Wenzhai. 2020. The Trp64Arg polymorphism in β3 adrenergic receptor (ADRB3) gene is associated with adipokines and plasma lipids: a systematic review, meta-analysis, and meta-regression. In Lipids in health and disease, 19, 99. doi:10.1186/s12944-020-01290-y. https://pubmed.ncbi.nlm.nih.gov/32430022/