| Autor: |
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 |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cell reports. 41(3) |
| ISSN: |
2211-1247 |
| Popis: |
Copper deficiency has emerged to be associated with various lipid metabolism diseases, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms that dictate the association between copper deficiency and metabolic diseases remain obscure. Here, we reveal that copper restoration caused by hepatic ceruloplasmin (Cp) ablation enhances lipid catabolism by promoting the assembly of copper-load SCO1-LKB1-AMPK complex. Overnutrition-mediated Cp elevation results in hepatic copper loss, whereas Cp ablation restores copper content to the normal level without eliciting detectable hepatotoxicity and ameliorates NAFLD in mice. Mechanistically, SCO1 constitutively interacts with LKB1 even in the absence of copper, and copper-loaded SCO1 directly tethers LKB1 to AMPK, thereby activating AMPK and consequently promoting mitochondrial biogenesis and fatty acid oxidation. Therefore, this study reveals a mechanism by which copper, as a signaling molecule, improves hepatic lipid catabolism, and it indicates that targeting copper-SCO1-AMPK signaling pathway ameliorates NAFLD development by modulating AMPK activity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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