m6A Regulates Liver Metabolic Disorders and Hepatogenous Diabetes
Autor: | Qingyang Zhang, Wei Li, Xin Tian, Guanshen Cui, Bao-Fa Sun, Yuhuan Li, Ying Yang, Fang Zhao |
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Rok vydání: | 2020 |
Předmět: |
0303 health sciences
medicine.medical_specialty RNA methylation Methyltransferase complex RNA Biology Carbohydrate metabolism medicine.disease Biochemistry 03 medical and health sciences Computational Mathematics 0302 clinical medicine Insulin resistance Endocrinology Internal medicine Diabetes mellitus Genetics medicine medicine.symptom Metabolic syndrome Molecular Biology Weight gain Gene 030217 neurology & neurosurgery 030304 developmental biology |
Zdroj: | Genomics, Proteomics & Bioinformatics. 18:371-383 |
ISSN: | 1672-0229 |
Popis: | N6-methyladenosine (m6A) RNA methylation is one of the most abundant modifications on mRNAs and plays an important role in various biological processes. The formation of m6A is catalysed by a methyltransferase complex containing a key factor methyltransferase-like 3 (Mettl3). However, the functions of Mettl3 and m6A modification in liver lipid and glucose metabolism remain unclear. Here, we show that both Mettl3 expression and m6A level increased in the liver of mice with High Fat Diet (HFD)-induced metabolic disorders, and overexpression of Mettl3 aggravated HFD-induced liver metabolic disorders and insulin resistance. Hepatocyte-specific knockout of Mettl3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain, reducing lipid accumulation and improving insulin sensitivity. Mechanistically, Mettl3 depletion-mediated m6A loss causes extended RNA half-lives of metabolism-related genes, consequently protects mice against HFD-induced metabolic syndrome. Our findings reveal a critical role of Mettl3-mediated m6A in HFD-induced metabolic disorders and hepatogenous diabetes. |
Databáze: | OpenAIRE |
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