Brown adipocyte activation mediates lipid metabolism through exosomal tRNA-derived fragments.

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. • Forskolin increases lipolysis in brown adipocyte. • Exosomal tRFs and tiRNAs is crucial for lipid metabolism under forskolin treatment. • tRF-Gly-GCC participate in lipolysis by downregulating UCHL1 expression. • tRF-Gly-GCC may provide potential diagnostic biomarkers for obesity treatment. [ABSTRACT FROM AUTHOR]