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bioRxiv · 10.1101/2021.03.04.433987

Identifying Dihydropyrimidine Dehydrogenase as a Novel Regulator of Hepatic Steatosis

Sullivan, K. E.·Kumar, S.·Zhang, Y.·de Koning, E.·Yuan, J.·Fan, F.
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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 (5-FU) administration. In an in vitro model of diet-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.

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Sullivan, K. E., Kumar, S., Zhang, Y., de Koning, E., Yuan, J., Fan, F.. 2021-03-04. Identifying Dihydropyrimidine Dehydrogenase as a Novel Regulator of Hepatic Steatosis. https://doi.org/10.1101/2021.03.04.433987

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