IRF8 aggravates nonalcoholic fatty liver disease via BMAL1/PPARγ axis
Non-alcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome arising from lipid metabolic imbalance, with its prevalence increasing globally. In this study, we observed a significant up-regulation of interferon regulatory factor 8 (IRF8) in the liver of NAFLD model mice and patients. Ov...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-05-01
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| Series: | Genes and Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304224001302 |
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| Summary: | Non-alcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome arising from lipid metabolic imbalance, with its prevalence increasing globally. In this study, we observed a significant up-regulation of interferon regulatory factor 8 (IRF8) in the liver of NAFLD model mice and patients. Overexpression of IRF8 induced lipid accumulation in the mouse primary hepatocytes. Mice with adeno-associated virus-mediated IRF8 overexpression exhibited hepatic steatosis due to up-regulated peroxisome proliferator-activated receptor γ (PPARγ) expression and increased fatty acid uptake and lipogenesis. In vitro, small interfering RNA-mediated IRF8 knockdown attenuated triglyceride accumulation by dampening PPARγ expression through transcriptional inhibition of brain and muscle ARNT-like 1. The PPARγ-specific antagonist GW9662 abolished the effect of IRF8 overexpression. Furthermore, adeno-associated virus-mediated IRF8 knockdown in the mouse liver markedly alleviated hepatic steatosis and obesity-related metabolic syndrome. These findings indicate that IRF8 plays a vital role in modulating hepatic lipid metabolism in a PPARγ-dependent manner and provide a previously unknown insight into NAFLD therapeutic strategies. |
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| ISSN: | 2352-3042 |