| First Author | Ni HM | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 12 | Pages | e115849 |
| PubMed ID | 25536043 | Mgi Jnum | J:225388 |
| Mgi Id | MGI:5693210 | Doi | 10.1371/journal.pone.0115849 |
| Citation | Ni HM, et al. (2014) Role of hypoxia inducing factor-1beta in alcohol-induced autophagy, steatosis and liver injury in mice. PLoS One 9(12):e115849 |
| abstractText | Chronic alcohol causes liver hypoxia and steatosis, which eventually develops into alcoholic liver disease (ALD). While it has been known that alcohol consumption activates hepatic hypoxia inducing factor-1alpha (HIF-1alpha), conflicting results regarding the role of HIF-1alpha in alcohol-induced liver injury and steatosis in mice have been reported. In the present study, we aimed to use hepatocyte-specific HIF-1beta knockout mice to eliminate the possible compensatory effects of the single knockout of the 1alpha subunit of HIF to study the role of HIFs in ALD. C57BL/6 wild type mice were treated with acute ethanol to mimic human binge drinking. Matched wild-type and hepatocyte specific HIF-1beta knockout mice were also subjected to a recently established Gao-binge alcohol model to mimic chronic plus binge conditions, which is quite common in human alcoholics. We found that acute alcohol treatment increased BNIP3 and BNIP3L/NIX expression in primary cultured hepatocytes and in mouse livers, suggesting that HIF may be activated in these models. We further found that hepatocyte-specific HIF-1beta knockout mice developed less steatosis and liver injury following the Gao-binge model or acute ethanol treatment compared with their matched wild type mice. Mechanistically, protection against Gao-binge treatment-induced steatosis and liver injury was likely associated with increased FoxO3a activation and subsequent induction of autophagy in hepatocyte-specific HIF-1beta knockout mice. |
