期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-021-23285-8
关键词
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资金
- National Key R&D Program of China [2018YFC1604404, 2018YFC1603002]
- National Natural Science Foundation of China [82030084, 81730083, 31771538, 81972757]
- Youth Innovation Promotion Association of Chinese Academy of Sciences fund [2017324]
- Sanofi-SIBS
- New World Group
- SIBS
- CAS-New World Joint Laboratory
Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease for which no drug treatment has been approved. This study shows that PPDPF inhibits the development of hepatic steatosis by negatively regulating mTORC1-S6K-SREBP1 signaling, suggesting a potential therapeutic candidate for NAFLD treatment.
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD. Non-alcoholic fatty liver disease (NAFLD) has become a prevalent chronic liver disease, however, drugs to treat this disease are still lacking. Here, the authors show that PPDPF inhibits the development of hepatic steatosis by negatively regulating mTORC1-S6K-SREBP1 signaling, which provides a potential therapeutic candidate for NAFLD treatment.
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