biostudies-literatureShen LSichuan Province Science and Technology Support ProgramChina Agricultural Research SystemNational Natural Science Foundation of China110820https://www.ebi.ac.uk/biostudies/studies/S-EPMC12648613biostudies-literatureUnknown301(12)tRNA-derived small RNAs (tsRNAs) are emerging regulators of metabolism, but their roles in adipose tissue are not well defined. Here, we profiled tsRNA expression in mouse brown adipose tissue (BAT), gonadal white adipose tissues, and inguinal white adipose tissue (iWAT), revealing depot-specific patterns and a notable enrichment of mitochondrial tRF-5c fragments, especially tRF-1:29-chrM.Ser-GCT (tRF^Ser-GCT), in BAT. tRF^Ser-GCT expression correlated with mitochondrial abundance and increased during adipogenic differentiation and metabolic activation, both in vivo and in vitro. Functionally, tRF^Ser-GCT promoted adipogenesis and lipid accumulation in 3T3-L1 cells and localized to mitochondria. Mechanistically, tRF^Ser-GCT is generated from mitochonThe Journal of biological chemistryRNase P generated tRF<sup>Ser-GCT</sup> promotes fat storage in adipocytes via Adrb2 signaling.PMC12648613323728442021ZDZX0008324210052024NSFSC02982021YFYZ000732573175Shen LChen LZhong YZhou XWang KZhao YZhao XChen DYang YZhu LLei YGan MLiao TNiu LWang XfalseRNase P generated tRF<sup>Ser-GCT</sup> promotes fat storage in adipocytes via Adrb2 signaling.tRNA-derived small RNAs (tsRNAs) are emerging regulators of metabolism, but their roles in adipose tissue are not well defined. Here, we profiled tsRNA expression in mouse brown adipose tissue (BAT), gonadal white adipose tissues, and inguinal white adipose tissue (iWAT), revealing depot-specific patterns and a notable enrichment of mitochondrial tRF-5c fragments, especially tRF-1:29-chrM.Ser-GCT (tRF^Ser-GCT), in BAT. tRF^Ser-GCT expression correlated with mitochondrial abundance and increased during adipogenic differentiation and metabolic activation, both in vivo and in vitro. Functionally, tRF^Ser-GCT promoted adipogenesis and lipid accumulation in 3T3-L1 cells and localized to mitochondria. Mechanistically, tRF^Ser-GCT is generated from mitochon2025-01-01T00:00:00Z2025 Oct2026-06-05T19:55:48.757Z2026-05-21T03:09:22.471ZS-EPMC126486134110150210.1016/j.jbc.2025.110820