| First Author | Zhang X | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 10 | Pages | 165854 |
| PubMed ID | 32502647 | Mgi Jnum | J:299800 |
| Mgi Id | MGI:6490684 | Doi | 10.1016/j.bbadis.2020.165854 |
| Citation | Zhang X, et al. (2020) The role of AMPKalpha2 in the HFD-induced nonalcoholic steatohepatitis. Biochim Biophys Acta Mol Basis Dis 1866(10):165854 |
| abstractText | Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic steatosis, inflammation and liver fibrosis and has become one of the leading causes of hepatocellular carcinoma and liver failure. However, the underlying molecular mechanism of hepatic steatosis and the progression to nonalcoholic steatohepatitis (NASH) are not fully understood. Herein, we discovered that AMPKalpha2 catalytic subunit showed reduced expression in the liver following high fat diet (HFD) feeding to mice. Importantly, knockout of AMPKalpha2 in mice aggravated NAFLD, hepatic steatosis, inflammation and fibrosis. On the other hand, hepatocyte-targeted overexpression of AMPKalpha2 prevented or reversed NAFLD indications. In vivo mechanistic studies revealed that increased phosphorylation of IKKalpha/beta and NF-kappaB in HFD-fed AMPKalpha2(-/-) mice compared to WT mice, and treatment of these mouse cohorts with an inhibitor of NF-kappaB signaling for 4 weeks, effectively attenuated the progression of steatohepatitis and metabolic disorder features. In summary, AMPKalpha2 provides a protective role in the process of hepatic steatosis to NASH progression through suppression of liver NF-kappaB signaling. |
