Integrated transcriptomic and translatomic exploration of the effect of betaine on lipid metabolic dysregulation induced by a high-fat diet

An excessive high-fat/energy diet is a major cause of obesity and associated complications, such as non-alcoholic fatty liver disease (NAFLD). Betaine has been shown to effectively improve hepatic lipid metabolism. However, the mechanistic basis for this improvement is largely unknown. Herein, integration of transcriptomics sequencing (RNA-seq) and ribosome footprints profiling (Ribo-seq) was used to investigate the means by which betaine alleviates hepatic lipid metabolic disorders induced by a high-fat diet. For the transcriptome, gene set enrichment analysis demonstrated betaine to reduce liver steatosis by up-regulation of fatty acid beta oxidation, lipid oxidation, and fatty acid catabolic processes. For the translatome, 574 differentially expressed genes were identified, 17 of which were associated with the NAFLD pathway. By combined analysis of RNA-seq and Ribo-seq, we found that betaine had the greatest effect on NAFLD at the translational level. Further, betaine decreased translational efficiency (TE) for IDI1, CYP5A1, TM7SF2, and APOA4, which are related to lipid biosynthesis. In summary, this study demonstrates betaine to alleviate lipid metabolic dysfunction at the translational level. The powerful multi-omics data integration approach used herein provides for a new understanding of the means by which to treat NAFLD. High-throughput sequencing of liver tissue from high-fat and betaine treated high-fat mice.