Fig. 5
ATF6 increase Sirt1 sulfhydration by promoting H2S production through upregulating CBS expression. ATF6 binds to the promotor region of CBS, a vital H2S producing enzyme in the liver, and promote the protein transcription. The upregulation of CBS enhances H2S production. Accumulation of H2S stimulates Sirt1 sulfhydrylation, then inhibits its downstream SREBP expression, to reduce lipogenesis and fatty acid beta-oxidation. In addition, Sirt1 sulfhydrylation decrease expression of pro-inflammatory factor IL-17A, and increase anti-inflammatory factor IL-10 expression. ATF6 could mitigate the liver lipogenesis and inflammation by stimulating sulfhydrylated Sirt1 through CBS/H2S pathway