Recently, the team of Wu Donghai, a researcher at the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, and Hui Xiaoyan, a professor at Hong Kong Chinese University, have revealed that androgen receptors negatively regulate beige fat cell activity by directly inhibiting the expression of PRDM16, a key molecule for beige fat activation. The study was published in Advanced Science. Zhao Shiting, Nie Tao and Li Lei are the co-first authors of the paper, and Hui Xiaoyan, Wu Donghai and Nie Tao are the co-corresponding authors.
Schematic diagram of the role and mechanism of androgen receptor negative regulation of beige fat cell activity. Photo courtesy of the research team
Obesity and a series of metabolic syndromes (including type 2 diabetes, cardiovascular and cerebrovascular diseases, fatty liver) are very harmful. In recent years, studies have found that white adipose tissue in adults can be transformed into “beige fat” under certain conditions, which can consume excess energy in the form of calories. Therefore, activating beige fat is currently the latest treatment method to fight obesity and metabolic diseases.
PRDM16 is a key transcription factor for the browning of white adipocytes. In this project, the researchers of the research group systematically analyzed the correlation between the total transcription factor profile (1600) and the expression level of PRDM16 through PRDM16 reporter mouse model and monoclonal screening technology, and found that androgen receptors showed the strongest negative correlation with PRDM16.
Experiments at the cell and animal levels further confirmed that the androgen receptor directly bound to the Prdm16 gene locus and inhibited its transcription and expression, and the activity of beige adipocytes in adip-specific knockout androgen receptor mice was enhanced. Mice with high androgen receptor expression by fat cells showed decreased beige. In addition, it is worth mentioning that this study also found that there are sex differences in the expression of PRDM16 in human adipose tissues – women have higher levels of PRDM16 expression than male individuals, which clinically confirms the inhibitory effect of androgens and their receptor pathways on PRDM16 and beige fat.
This work confirms the negative regulatory role of androgen receptors in beige adipocytes from many aspects, and provides a new perspective for understanding the sex differences of adipose tissue.
The above research has been supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China-Youqing Program (Hong Kong and Macao), the National Natural Science Foundation of China, the Hong Kong General Research Fund, the Chinese Academy of Sciences International Cooperation Project, and the China-New Zealand Joint Laboratory of Biomedicine and Health. (Source: China Science News, Zhu Hanbin, Zhao Shiting)
Related paper information:https://doi.org/10.1002/advs.202300070
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