PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling.
Nat Commun
; 12(1): 3059, 2021 05 24.
Article
en En
| MEDLINE
| ID: mdl-34031390
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Péptidos y Proteínas de Señalización Intracelular
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Hígado Graso
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Serina-Treonina Quinasas TOR
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Hígado
Límite:
Animals
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Humans
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Male
Idioma:
En
Año:
2021
Tipo del documento:
Article