Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice

BACKGROUND: Although salt plays an important role in maintaining the normal physiological metabolism of the human body, many abnormalities in the liver caused by a high-salt diet, especially with normal pathological results, are not well characterized. METHODS: Eight-week-old female C57BL/6 mice were randomly divided into a normal group and a high salt group. These groups were then fed with normal or sodium-rich chow (containing 6% NaCl) for 6 weeks. Liver injury was evaluated, and the influences of a high-salt diet on the liver were analyzed by transcriptome sequencing at the end of week 6. RESULTS: We found that although no liver parenchymal injury could be found after high-salt feeding, many metabolic abnormalities had formed based on transcriptome sequencing results. GO and KEGG enrichment analyses of differentially expressed genes revealed that at least 15 enzymatic activities and the metabolism of multiple substances were affected by a high-salt diet. Moreover, a variety of signaling and metabolic pathways, as well as numerous biological functions, were involved in liver dysfunction due to a high-salt diet. This included some known pathways and many novel ones, such as retinol metabolism, linoleic acid metabolism, steroid hormone biosynthesis, and signaling pathways. CONCLUSIONS: A high-salt diet can induce serious abnormal liver metabolic activities in mice at the transcriptional level, although substantial physical damage may not yet be visible. This study, to our knowledge, was the first to reveal the impact of a high-salt diet on the liver at the omics level, and provides theoretical support for potential clinical risk evaluation, pathogenic mechanisms, and drug design for combating liver dysfunction. This study also provides a serious candidate direction for further research on the physiological impacts of high-salt diets.