Open AccessChronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice
Author(s) -
Yasuyo Urasaki,
Giuseppe Pizzorno,
Thuc T. Le
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0146994
Subject(s) - uridine , gluconeogenesis , fatty liver , endocrinology , medicine , nucleoside , lipid metabolism , pyrimidine metabolism , oral administration , metabolism , biology , chemistry , pharmacology , biochemistry , gene , enzyme , rna , purine , disease
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.