Brown/beige adipocyte activation triggers adipose thermogenesis, which is crucial for maintaining homeostasis in the body as it helps regulate glucose metabolism, reduce fat accumulation, and enhance insulin sensitivity. However, the underlying mechanisms remain unclear. Thus, our research aims to identify the master regulator for brown/beige activation and non-dependent UCP1 thermogenesis. Using engineered Cas9 activation complexes to explore the transcriptional activation of thermogenesis using single-guide RNA, we discovered Fas apoptosis inhibitory molecule (FAIM) as the top candidate. Previous studies have demonstrated that FAIM is negatively correlated with BMI and obesity and is highly expressed in brown adipocytes compared to white adipocytes. Interestingly, our further validation using ERthermAC dye showed that thermogenesis is highly activated in FAIM-overexpressed white adipocytes. Moreover, RT-qPCR showed that the thermogenic marker UCP1, browning marker CIDEA and glucose uptake marker Glut1 are increased in FAIM-overexpressed white adipocytes. Collectively, our study proves that FAIM is essential in the regulation of browning, glucose, and thermogenesis. Therefore, targeting FAIM poses a good strategy to combat obesity and type 1 and 2 diabetes.
L. Noriega: None. C. Wang: None.
