Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex

• DOI: 10.1016/j.celrep.2022.111498
• Publication Date: 2022-10-18T15:31:15Z
• Authors: Liping Xie; Yanmei Yuan; Simiao Xu; Sijia Lu; Jinyang Gu; Yanping Wang; Yibing Wang; Xianjing Zhang; Suzhen Chen; Jian Li; Junxi Lu; Honglin Sun; Ruixiang Hu; Hailong Piao; Wen Wang; Cunchuan Wang; Jing Wang; Na Li; Morris F. White; Liu Han; Weiping Jia; Ji Miao; Junli Liu
• Keywords: Ceruloplasmin; Catabolism; Copper deficiency

Copper deficiency has emerged to be associated with various lipid metabolism diseases, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms that dictate association between copper and metabolic diseases remain obscure. Here, we reveal restoration caused by hepatic ceruloplasmin (Cp) ablation enhances catabolism promoting assembly of copper-load SCO1-LKB1-AMPK complex. Overnutrition-mediated Cp elevation results in loss, whereas restores content normal level without eliciting detectable hepatotoxicity ameliorates NAFLD mice. Mechanistically, SCO1 constitutively interacts LKB1 even absence copper, copper-loaded directly tethers AMPK, thereby activating AMPK consequently mitochondrial biogenesis acid oxidation. Therefore, this study reveals a mechanism which as signaling molecule, improves catabolism, it indicates targeting copper-SCO1-AMPK pathway development modulating activity.