Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice

PloS One
Yasuyo UrasakiThuc T Le

Abstract

Uridine is a pyrimidine nucleoside that exerts restorative functions in tissues under stress. Short-term co-administration of uridine with multiple unrelated drugs prevents drug-induced liver lipid accumulation. Uridine has the ability to modulate liver metabolism; however, the precise mechanism has not been delineated. In this study, long-term effects of uridine on liver metabolism were examined in both HepG2 cell cultures and C57BL/6J mice. We report that uridine administration was associated with O-GlcNAc modification of FOXO1, increased gluconeogenesis, reduced insulin signaling activity, and reduced expression of a liver-specific fatty acid binding protein FABP1. Long-term uridine feeding induced systemic glucose intolerance and severe liver lipid accumulation in mice. Our findings suggest that the therapeutic potentials of uridine should be designed for short-term acute administration.

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Citations

Mar 18, 2017·Science·Yingfeng DengPhilipp E Scherer
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Methods Mentioned

BETA
acetylation
glycosylation
transfection
immunoprecipitation
electrophoresis
X-ray

Software Mentioned

Excels

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