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Uncovering the roles of dihydropyrimidine dehydrogenase in fatty-acid induced steatosis using human cellular models
- Source :
- Scientific Reports, Vol 12, Iss 1, Pp 1-16 (2022)
- Publication Year :
- 2022
- Publisher :
- Nature Portfolio, 2022.
-
Abstract
- Abstract Pyrimidine catabolism is implicated in hepatic steatosis. Dihydropyrimidine dehydrogenase (DPYD) is an enzyme responsible for uracil and thymine catabolism, and DPYD human genetic variability affects clinically observed toxicity following 5-Fluorouracil administration. In an in vitro model of fatty acid-induced steatosis, the pharmacologic inhibition of DPYD resulted in protection from lipid accumulation. Additionally, a gain-of-function mutation of DPYD, created through clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) engineering, led to an increased lipid burden, which was associated with altered mitochondrial functionality in a hepatocarcionma cell line. The studies presented herein describe a novel role for DPYD in hepatocyte metabolic regulation as a modulator of hepatic steatosis.
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 12
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.08b75c00d73b42f58c51d8a6d2753658
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41598-022-17860-2