title: Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice.
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.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Roseman University of Health Sciences, 10530 Discovery Drive, Las Vegas, Nevada, 89135, United States of America.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Urasaki
authors.affiliation: Desert Research Institute, 10530 Discovery Drive, Las Vegas, Nevada, 89135, United States of America.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pizzorno
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Roseman University of Health Sciences, 10530 Discovery Drive, Las Vegas, Nevada, 89135, United States of America.
authors.forename: Thuc T
authors.initials: TT
authors.lastname: Le
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects*; D018149:Glucose Intolerance / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D011236:Prediabetic State / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D014529:Uridine / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D014529:Uridine