The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila
Summary: 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 t...
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724014505 |
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| author | Lihong Sheng Jianpeng Gao Qingyuan Wei Ye Gong Zhi-Xiang Xu |
| author_facet | Lihong Sheng Jianpeng Gao Qingyuan Wei Ye Gong Zhi-Xiang Xu |
| author_sort | Lihong Sheng |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-6943bf76f7c340a097d259a8b45a270e |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-6943bf76f7c340a097d259a8b45a270e2025-08-20T01:57:21ZengElsevierCell Reports2211-12472025-01-0144111509910.1016/j.celrep.2024.115099The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in DrosophilaLihong Sheng0Jianpeng Gao1Qingyuan Wei2Ye Gong3Zhi-Xiang Xu4Department 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; Corresponding authorDepartment 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, ChinaDepartment 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, ChinaDepartment 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; Corresponding authorDepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724014505CP: MetabolismCP: Neuroscience |
| spellingShingle | Lihong Sheng Jianpeng Gao Qingyuan Wei Ye Gong Zhi-Xiang Xu The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila Cell Reports CP: Metabolism CP: Neuroscience |
| title | The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila |
| title_full | The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila |
| title_fullStr | The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila |
| title_full_unstemmed | The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila |
| title_short | The glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila |
| title_sort | glial udp glycosyltransferase ugt35b regulates longevity by maintaining lipid homeostasis in drosophila |
| topic | CP: Metabolism CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724014505 |
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