Dlat, short for dihydrolipoamide S-acetyltransferase, is a key enzyme in the pyruvate dehydrogenase complex (PDHc). It plays a crucial role in the conversion of pyruvate to acetyl-CoA, connecting glycolysis to the tricarboxylic acid (TCA) cycle, thus being vital for energy metabolism in cells. Genetic models, such as knockout (KO) mice, are valuable for studying its functions [1-10].

Ablation of Dlat significantly attenuated hyperforin-mediated adipose tissue browning both in vitro and in vivo, suggesting Dlat is involved in a non-canonical thermogenesis pathway through its interaction with Trpv3, activating AMPK and promoting Ucp1-dependent adipose thermogenesis [1,4]. In cancer research, in hepatocellular carcinoma (HCC), knockdown of Dlat-related functions may inhibit tumor growth as it promotes leucine accumulation and mTOR complex activation by acetylating AUH, a leucine catabolism enzyme [2]. Also, in triple-negative breast cancer (TNBC), inhibition of the DLAT-YAP1 interaction might impede cancer progression as DLAT promotes TNBC malignancy via YAP1 activation [3].

In conclusion, Dlat is essential for energy metabolism-related pathways. Studies using gene knockout models have revealed its significance in obesity and various cancers, such as HCC and TNBC. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Chen, Suzhen, Liu, Xiaoxiao, Peng, Chao, Han, Junfeng, Liu, Junli. . The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity. In Cell metabolism, 33, 565-580.e7. doi:10.1016/j.cmet.2021.02.007. https://pubmed.ncbi.nlm.nih.gov/33657393/

2. Wang, Ning, Lu, Sijia, Cao, Ziyi, Chen, Suzhen, Liu, Junli. 2025. Pyruvate metabolism enzyme DLAT promotes tumorigenesis by suppressing leucine catabolism. In Cell metabolism, , . doi:10.1016/j.cmet.2025.02.008. https://pubmed.ncbi.nlm.nih.gov/40112809/

3. Liu, Diya, Wang, Xuehui, Qian, Fengyuan, Deng, Xiaochong, Fang, Lin. 2024. DLAT promotes triple-negative breast cancer progression via YAP1 activation. In Cancer biology & therapy, 25, 2421578. doi:10.1080/15384047.2024.2421578. https://pubmed.ncbi.nlm.nih.gov/39460738/

4. Lu, Sijia, Jiang, Quanxin, Zhou, Peihui, Liu, Junli, Chen, Suzhen. 2024. Targeting Dlat-Trpv3 pathway by hyperforin elicits non-canonical promotion of adipose thermogenesis as an effective anti-obesity strategy. In Journal of advanced research, , . doi:10.1016/j.jare.2024.11.035. https://pubmed.ncbi.nlm.nih.gov/39631519/