GSE183584
Salt induces hepatic inflammatory response through epigenetic modulation of SIRT3 [RNA-seq]
Purpose: Although clinical evidence suggests that high salt intake is associated with NAFLD, the underlying mechanism remains elusive. We sought to investigate whether salt-induced inflammation in liver is dependent on SIRT3 reduction. Methods: 6-week-old male SIRT3 knockout or their wild-type littermates were fed with high salt diet (HSD, containing 8% NaCl) or normal salt diet (NSD, containing 0.4% NaCl) for 4 months. And then their liver tissues were removed and total RNA was extracted to perform RNA sequencing. Results: 1850 differentially upregulated expressed genes were identified when comparing HSD group (HSD1, HSD2) to NSD group (NSD WT1, NSD2). Meanwhile, 1246 differentially upregulated expressed genes in response to SIRT3 knockout were determined (each group containing 3 samples). we observed that the common genes upregulated by both HSD and knockout of SIRT3 were enriched in immune system, including Tnf, Ccl2, etc. In addition, the common genes upregulated by knockout of SIRT3 in both NSD and HSD group were still enriched in the immune system. Conclusions: Through RNA-seq, we determined that HSD-induced hepatic inflammtion was highly similar to the effect of SIRT3 knockout, suggesting that reduction of SIRT3 expression is the main reason leading to salt-induced hepatic inflammation. Overall design: Including 15 samples, liver mRNA profiles of SIRT3 knockout (KO) or wild-type (WT) mice fed with high salt diet (HSD) or normal salt diet (NSD) for 4 months.