棕色脂肪细胞激活通过外泌体 tRNA 衍生片段介导脂质代谢。
Brown adipocyte activation mediates lipid metabolism through exosomal tRNA-derived fragments.
机构信息
Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
出版信息
Biochem Biophys Res Commun. 2023 Sep 10;672:128-136. doi: 10.1016/j.bbrc.2023.06.038. Epub 2023 Jun 19.
Human obesity is related with intrinsic impairments of adipocyte lipolysis and ectopic lipid accumulation. Small regulatory RNAs, such as tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), are enriched in exosomes and play a crucial role in lipid metabolism. To determine certain tRFs for lipolysis, brown adipocytes were treated with forskolin. Using tRFs sequencing, 207 different expressed exosomal tRFs were determined. In forskolin samples, 145 downregulated and 62 upregulated tRFs were identified. Further, qRT-PCR validated that three notably upregulated tRFs (tRF-Gly-GCC-007, tRF-Gly-GCC-008, and tRF-Gly-GCC-009) were in accordance with the sequencing result. Target genes of tRFs were involved in positive regulation of protein phosphorylation and cell adhesion process by significantly downregulating UCHL1 expression, which might participate in lipolysis. This study might provide therapeutic targets and potential diagnostic biomarkers for obesity treatment.
人类肥胖与脂肪细胞脂肪分解和异位脂质积累的内在损伤有关。小调节 RNA，如 tRNA 衍生片段（tRFs）和 tRNA 半分子（tiRNAs），富含于外泌体中，在脂质代谢中发挥着关键作用。为了确定脂肪分解的特定 tRFs，用 forskolin 处理棕色脂肪细胞。通过 tRFs 测序，确定了 207 种不同表达的外泌体 tRFs。在 forskolin 样本中，鉴定出 145 个下调和 62 个上调的 tRFs。进一步的 qRT-PCR 验证表明，三个明显上调的 tRFs（tRF-Gly-GCC-007、tRF-Gly-GCC-008 和 tRF-Gly-GCC-009）与测序结果一致。tRFs 的靶基因通过显著下调 UCHL1 表达，参与正向调节蛋白磷酸化和细胞黏附过程，可能参与脂肪分解。本研究可能为肥胖症治疗提供治疗靶点和潜在的诊断生物标志物。
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