Dgat1, short for diacylglycerol-acyltransferase 1, is a key enzyme in lipid metabolism. It catalyzes the final step in triglyceride synthesis by converting diacylglycerol and acyl-CoA to triglyceride, playing a crucial role in lipid droplet formation and lipid homeostasis [1,2,3,4,5,7]. It is involved in multiple biological pathways related to fat metabolism, and its dysregulation has implications for various diseases [1,2,5,6,8,9]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its function.

In glioblastoma (GBM), inhibiting Dgat1 disrupted lipid homeostasis, leading to excessive fatty acids moving into mitochondria for oxidation, generating high levels of reactive oxygen species (ROS), mitochondrial damage, and apoptosis. This demonstrated that Dgat1 upregulation in GBM protects from oxidative damage and maintaining lipid homeostasis, and targeting Dgat1 could be a promising therapeutic approach [1]. In clear cell renal cell carcinoma (ccRCC), pharmacological inhibition or depletion of Dgat1 inhibited lipid droplet formation in vitro and ccRCC tumorigenesis in vivo, indicating the JMJD6-Dgat1 axis as a potential new therapeutic target [2]. In the context of starvation-induced autophagy, mTORC1-regulated autophagy is necessary and sufficient for starvation-induced lipid droplet biogenesis mediated by Dgat1, which channels autophagy-liberated fatty acids into new lipid droplets to protect mitochondrial function [3].

In conclusion, Dgat1 is essential for lipid homeostasis and triglyceride synthesis. Through model-based research, especially KO/CKO mouse models, its role in diseases like glioblastoma and ccRCC has been revealed. Understanding Dgat1's function provides potential therapeutic strategies for these and other diseases related to lipid metabolism dysregulation [1,2].