Hepatic HuR modulates lipid homeostasis in response to high-fat diet.
Nat Commun
; 11(1): 3067, 2020 06 16.
Article
em En
| MEDLINE
| ID: mdl-32546794
ABSTRACT
Lipid transport and ATP synthesis are critical for the progression of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) forms complexes with NAFLD-relevant transcripts. It associates with intron 24 of Apob pre-mRNA, with the 3'UTR of Uqcrb, and with the 5'UTR of Ndufb6 mRNA, thereby regulating the splicing of Apob mRNA and the translation of UQCRB and NDUFB6. Hepatocyte-specific HuR knockout reduces the expression of APOB, UQCRB, and NDUFB6 in mice, reducing liver lipid transport and ATP synthesis, and aggravating high-fat diet (HFD)-induced NAFLD. Adenovirus-mediated re-expression of HuR in hepatocytes rescues the effect of HuR knockout in HFD-induced NAFLD. Our findings highlight a critical role of HuR in regulating lipid transport and ATP synthesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metabolismo dos Lipídeos
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Dieta Hiperlipídica
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Hepatopatia Gordurosa não Alcoólica
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Proteína Semelhante a ELAV 1
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Fígado
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article