Sheng Lihong, Gao Jianpeng, Wei Qingyuan, Gong Ye, Xu Zhi-Xiang
Department of Critical Care Medicine and Neurosurgery of Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Department of Critical Care Medicine and Neurosurgery of Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Cell Rep. 2025 Jan 28;44(1):115099. doi: 10.1016/j.celrep.2024.115099. Epub 2024 Dec 24.
Lipid droplets (LDs) are dynamic organelles essential for lipid storage and organismal survival. Studies have highlighted the importance of glial function in brain LD formation during aging; however, the genes and mechanisms involved remain elusive. Here, we found that Ugt35b, a member of the uridine diphosphate (UDP)-glycosyltransferases that catalyze the transfer of glycosyl groups to acceptors, is highly expressed in glia and crucial for Drosophila lifespan. By integrating multiomics data, we demonstrated that glial Ugt35b plays key roles in regulating glycerolipid and glycerophospholipid metabolism in the brain. Notably, we found that Ugt35b and Lsd-2 are co-expressed in glia and confirmed their protein interaction in vivo. Knockdown of Ugt35b significantly reduced LD formation by downregulating Lsd-2 expression, while overexpression of Lsd-2 partially rescued the shortened lifespan in glial Ugt35b RNAi flies. Our findings reveal the crucial role of glial Ugt35b in regulating LD formation to maintain brain lipid homeostasis and support Drosophila lifespan.
脂滴（LDs）是对脂质储存和生物体存活至关重要的动态细胞器。研究强调了神经胶质细胞功能在衰老过程中脑内脂滴形成中的重要性；然而，所涉及的基因和机制仍不清楚。在这里，我们发现Ugt35b是尿苷二磷酸（UDP）-糖基转移酶家族的一员，可催化糖基转移至受体，它在神经胶质细胞中高度表达，对果蝇寿命至关重要。通过整合多组学数据，我们证明神经胶质细胞中的Ugt35b在调节脑内甘油olipid和甘油磷脂代谢中起关键作用。值得注意的是，我们发现Ugt35b和Lsd-2在神经胶质细胞中共表达，并在体内证实了它们的蛋白质相互作用。敲低Ugt35b可通过下调Lsd-2表达显著减少脂滴形成，而Lsd-2的过表达部分挽救了神经胶质细胞Ugt35b RNA干扰果蝇缩短的寿命。我们的研究结果揭示了神经胶质细胞Ugt35b在调节脂滴形成以维持脑脂质稳态和支持果蝇寿命方面的关键作用。
