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FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation
- Source :
- Journal of Cellular Biochemistry. 119:5676-5685
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Fat mass and obesity-associated protein (FTO) is a RNA demethylase, whether FTO regulates fat metabolism through its demethylation is unclear. The results of this study confirmed that N6-methyladenosine (m6 A) is associated with fat accumulation both in vivo and in vitro. The data showed that FTO down-regulated m6 A levels, decreased mitochondrial content, and increased triglyceride (TG) deposition. However, an FTO (R316A) mutant lacking demethylation activity could not regulate mitochondria and TG content, indicating that FTO affects mitochondrial content and fat metabolism by modulating m6 A levels in hepatocytes. In addition, the regulatory roles of cycloleucine (methylation inhibitor) and betaine (methyl donor) could regulate m6 A levels and fat deposition. This work clarified that the demethylation function of FTO plays an essential role in the fat metabolism of hepatocytes and links the epigenetic modification of RNA with fat deposition, thereby providing a new target (m6 A) for regulation of hepatic fat metabolism.
- Subjects :
- 0301 basic medicine
Protein Conformation
Swine
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Mitochondrion
Methylation
Biochemistry
Epigenesis, Genetic
Fats
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Animals
Humans
Cycloleucine
Molecular Biology
Demethylation
Lipotropic Agents
biology
Triglyceride
nutritional and metabolic diseases
RNA
Lipid metabolism
Hep G2 Cells
Cell Biology
Lipid Metabolism
Mitochondria
Cell biology
Betaine
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Hepatocytes
biology.protein
Demethylase
Subjects
Details
- ISSN :
- 10974644 and 07302312
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....eea5e944efb23376cce2a88ee715a809