Abstract
tRNA-derived fragments (tRFs), a novel type of non-coding RNA derived from tRNAs, play an important part in governing gene expressions at a post-transcriptional level. To date, the regulatory mechanism of tRFs governing fat deposition and adipogenesis is completely unknown. In this study, high fat diet was employed to induce an obese rat model, and tRFs transcriptome sequencing was conducted to identify differentially expressed tRFs that response to obesity. We found out that tRFGluTTC, which promoted preadipocyte proliferation by increasing expressions of cell cycle regulatory factors, had the highest fold change in the 296 differentially expressed tRFs. Moreover, tRFGluTTC also suppressed preadipocyte differentiation by reducing triglyceride content and lipid accumulation, and by decreasing expressions of genes that related to fatty acid synthesis. According to results of luciferase activity analysis, tRFGluTTC directly targeted Kruppel-like factor (KLF) 9, KLF11, and KLF12, thus significantly suppressing mRNA expressions of these target genes. Moreover, tRFGluTTC suppressed adipogenesis, accompanying by suppressing expressions of adipogenic transcription factors (aP2, PPARγ, and C/EBPα). In conclusion, these results imply that tRFGluTTC may act as a novel epigenetic molecule regulating adipogenesis and could provide a new strategy for the intervention treatment of obesity.
Highlights
Epidemic obesity is seriously affecting humans’ health worldwide
Obesity can lead to adipose tissue mass increase, and advance the size and number of adipocytes differentiated from preadipocytes at cellular level [2]
The complex process of preadipocyte differentiation is regulated by sequential activations of multifarious transcription factors, such as PPARγ, C/EBPa (CCAAT enhancer binding protein alpha), and KLF (Kruppel-like factor) family [2,3,4]
Summary
Obesity is associated with high occurrence risks of multiple diseases, such as cardiovascular disease, type II diabetes, hypertension, respiratory disease, and a variety of cancers [1]. Obesity can lead to adipose tissue mass increase, and advance the size and number of adipocytes differentiated from preadipocytes at cellular level [2]. To understand obesity and its associated diseases, exploring potential molecular mechanisms governing adipocyte differentiation is necessary. The complex process of preadipocyte differentiation is regulated by sequential activations of multifarious transcription factors, such as PPARγ (peroxisome proliferator-activated receptor gamma), C/EBPa (CCAAT enhancer binding protein alpha), and KLF (Kruppel-like factor) family [2,3,4]. Our knowledge about transcription factors and molecular switches regulating adipocyte differentiation is far from complete
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