Salt induces hepatic inflammatory response through epigenetic modulation of SIRT3 [ChIP-seq]

ABSTRACT: Purpose: Our previous study has confirmed that reduction of SIRT3 expression is a main factor contributing to salt-induced hepatic inflammtion. Here we sought to investigate whether salt-induced SIRT3 reduction was related to epigenetic modification. 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 subjected to ChIP-seq using antibodies against H3K27ac (ab4729), H3K4me1 (ab8895), H3K9ac (39917) and H3 (ab1791). Results: Through ChIP-seq, we observed the enrichment of H3K27ac was increased on the promoters of Sirt3 and some pro-inflammatory genes, including Ccl2, Tnf and Il6, after high salt loading. However, neither H3K4me1 nor H3K9ac displayed such phenomunum. In addition, those genes containing increased H3K27ac level in response to high salt were mainly enriched in metabolism and inflammatory pathways. And knockout of SIRT3 mainly affected genes related to AMP-activated protein kinase (AMPK) and insulin signaling pathways. Conclusions: Salt-induced SIRT3 reduction is related to the epigenetic regulation, especially H3K27ac.

ORGANISM(S): Mus musculus

PROVIDER: GSE183582 | GEO | 2023/09/01

REPOSITORIES: GEO