A novel tRF-Gly is associated with obesity development through post-transcriptional regulation of lipid metabolism

作者：Yuhang Lei, Mailin Gan, Kai Wang, Tianci Liao, Yiting Yang, Xue Zhao, Xin Zhang, Dujun Chen, Xinyi Wang, Jianfeng Ma, Lili Niu, Ye Zhao, Lei Chen, Xiaofeng Zhou, Yan Wang, Mingzhou Li, Li Zhu, Linyuan Shen · 发表于：Cellular & Molecular Biology Letters · 年份：2025 · DOI：10.1186/s11658-025-00835-2 · 被引用次数：1 · 研究领域：Glycosylation and Glycoproteins Research、Wnt/β-catenin signaling in development and cancer、Lipid metabolism and biosynthesis

BACKGROUND: Obesity, characterized by excessive fat accumulation, represents a global health crisis closely linked to metabolic disorders such as type 2 diabetes, hypertension, and atherosclerosis. tRNA-derived small RNAs (tsRNAs) have recently emerged as important epigenetic regulators, yet their roles in fat deposition remain poorly characterized. This study aims to identify tsRNAs that influence fat accumulation and to elucidate their molecular mechanisms, with a focus on tRF‑Gly‑GCC‑037 (tRF‑Gly) as a candidate regulator of adipocyte differentiation. METHODS: Visceral adipose tissue was collected from obese and lean pigs for comprehensive tRF and tiRNA sequencing. Differential expression analysis identified tRF‑Gly as a highly abundant candidate in obese samples. Functional assays in 3T3‑L1 preadipocytes included both overexpression and knockdown of tRF‑Gly, followed by lipid accumulation measurements and assessment of key adipogenic markers (CEBPα and PPARγ) by quantitative real-time PCR (qRT‑PCR) and western blot. Mechanistically, dual‑luciferase reporter assays, RNA immunoprecipitation (RIP), and nuclear-cytoplasmic protein fractionation were performed to examine how tRF‑Gly modulates the RAC1/JNK2/β‑catenin signaling axis. RESULTS: tRF‑Gly was significantly upregulated in visceral adipose tissue from obese pigs and ranked among the most abundant tsRNAs. Overexpression of tRF‑Gly in 3T3‑L1 cells and in C57BL/6 mice promoted lipid accumulation and increased CEBPα and PP...