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In addition, overexpression of SIRT6 increased NRF2 and its target genes expression, and knockdown of SIRT6 decreased NRF2 and its target genes expression. Meanwhile, knockdown of SIRT6 inhibited NRF2 nucleus protein expression. Further, knockdown of SIRT6 decreased phosphorylation of NRF2, overexpression of SIRT6 increased phosphorylation of NRF2. SIRT6 interacted with NRF2. In vivo, the levels of TNF-α and IL-1β were increased in the serum of hyperlipidemia mice. Hyperlipidemia-induced production of MCP-1, IL-6 and IL-1β was significan