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

PLoS ONE

Volumn 11, Issue 1, 2016, Pages

  Urasaki, Yasuyo ^a   Pizzorno, Giuseppe ^b   Le, Thuc T ^a  

^a ROSEMAN UNIVERSITY OF HEALTH SCIENCES   (United States)

^b DESERT RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID BINDING PROTEIN; FATTY ACID BINDING PROTEIN 1; INSULIN; TRANSCRIPTION FACTOR FKHR; UNCLASSIFIED DRUG; URIDINE; FORKHEAD TRANSCRIPTION FACTOR; FOXO1 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL CULTURE; CHRONIC DRUG ADMINISTRATION; CONTROLLED STUDY; FATTY LIVER; GLUCONEOGENESIS; GLUCOSE INTOLERANCE; HEPG2 CELL LINE; IMPAIRED GLUCOSE TOLERANCE; LIPID STORAGE; LIVER METABOLISM; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN MODIFICATION; SIGNAL TRANSDUCTION; ANIMAL; CHEMICALLY INDUCED; DRUG EFFECTS; HEP-G2 CELL LINE; HUMAN; METABOLISM; PATHOLOGY;

ANIMALS; FATTY LIVER; FORKHEAD BOX PROTEIN O1; FORKHEAD TRANSCRIPTION FACTORS; GLUCONEOGENESIS; GLUCOSE INTOLERANCE; HEP G2 CELLS; HUMANS; MICE; PREDIABETIC STATE; URIDINE;

EID: 84958212031     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0146994     Document Type: Article

References (37)

1. McEvilly M, Popelas C, Tremmel B. Use of uridine triacetate for the management of fluorouracil overdose. Am J Health Syst Pharm 2011; 68(19):1806-. doi: 10.2146/ajhp100434 PMID: 21930638
2. McComsey GA, Walker UA, Budhathoki CB, Su Z, Currier JS, Kosmiski L, et al. Uridine supplementation in the treatment of HIV lipoatrophy: results of ACTG 5229. Aids 2010; 24(16):2507-15. doi: 10. 1097/QAD.0b013e32833ea9bc PMID: 20827170
3. Wurtman RJ. A nutrient combination that can affect synapse formation. Nutrients 2014; 6(4):1701-10. doi: 10.3390/nu6041701 PMID: 24763080
4. Gallai V, Mazzotta G, Montesi S, Sarchielli P, Del Gatto F. Effects of uridine in the treatment of diabetic neuropathy: an electrophysiological study. Acta Neurol Scand 1992; 86(1):3-7. PMID: 1325728
5. Lebrecht D, Vargas-Infante YA, Setzer B, Kirschner J, Walker UA. Uridine supplementation antagonizes zalcitabine-induced microvesicular steatohepatitis in mice. Hepatology 2007; 45(1):72-9. PMID: 17187420
6. Le TT, Urasaki Y, Pizzorno G. Uridine prevents fenofibrate-induced fatty liver. PLoS ONE 2014; 9(1): e87179. doi: 10.1371/journal.pone.0087179 PMID: 24475249
7. Le TT, Urasaki Y, Pizzorno G. Uridine prevents tamoxifen-induced liver lipid droplet accumulation. BMC Pharmacol Toxicol 2014; 15:27. doi: 10.1186/2050-6511-15-27 PMID: 24887406
8. Connolly GP, Duley JA. Uridine and its nucleotides: biological actions, therapeutic potentials. Trends Pharmacol Sci 1999; 20(5):218-25. PMID: 10354618
9. Evans DR, Guy HI. Mammalian pyrimidine biosynthesis: fresh insights into an ancient pathway. J Biol Chem 2004; 279(32):33035-8. PMID: 15096496
10. Loffler M, Jockel J, Schuster G, Becker C. Dihydroorotat-ubiquinone oxidoreductase links mitochondria in the biosynthesis of pyrimidine nucleotides. Mol Cell Biochem 1997; 174(1-2):125-9. PMID: 9309676
11. Loffler M, Fairbanks LD, Zameitat E, Marinaki AM, Simmonds HA. Pyrimidine pathways in health and disease. Trends Mol Med 2005; 11(9):430-7. PMID: 16098809
12. Hawkins M, Angelov I, Liu R, Barzilai N, Rossetti L. The tissue concentration of UDP-N-Acetylglucosamine modulates the stimulatory effect of insulin on skeletal muscle glucose uptake. J Biol Chem 1997; 272(8):4889-95. PMID: 9030547
13. Yamamoto T, Inokuchi T, Ka T, Yamamoto A, Takahashi S, Tsutsumi Z, et al. Relationship between plasma uridine and insulin resistance in patients with non-insulin-dependent diabetes mellitus. Nucleosides Nucleotides Nucleic Acids 2010; 29(4-6):504-8. doi: 10.1080/15257771003740986 PMID: 20544544
14. Dudzinska W, Lubkowska A, Jakubowska K, Suska M, Skotnicka E. Insulin resistance induced by maximal exercise correlates with a post-exercise increase in uridine concentration in the blood of healthy young men. Physiol Res 2013; 62(2):163-70. PMID: 23234409
15. Urasaki Y, Pizzorno G, Le TT. Uridine affects liver protein glycosylation, insulin signaling, and heme biosynthesis. PLoS One 2014; 9(6):e99728. doi: 10.1371/journal.pone.0099728 PMID: 24918436
16. Urasaki Y, Johlfs MG, Fiscus RR, Le TT. Imaging immune and metabolic cells of visceral adipose tissues with multimodal nonlinear optical microscopy. PLoS One 2012; 7(6):e38418. doi: 10.1371/journal. pone.0038418 PMID: 22701636
17. Le TT, Ziemba A, Urasaki Y, Brotman S, Pizzorno G. Label-free evaluation of hepatic microvesicular steatosis with multimodal coherent anti-Stokes Raman scattering microscopy. PLoS One 2012; 7(11): e51092. doi: 10.1371/journal.pone.0051092 PMID: 23226469
18. Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, et al. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 2003; 423(6939):550-5. PMID: 12754525
19. I OS, Zhang W, Wasserman DH, Liew CW, Liu J, Paik J, et al. FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization. Nat Commun 2015; 6:7079. doi: 10.1038/ncomms8079 PMID: 25963540
20. Housley MP, Rodgers JT, Udeshi ND, Kelly TJ, Shabanowitz J, Hunt DF, et al. O-GlcNAc regulates FoxO activation in response to glucose. J Biol Chem 2008; 283(24):16283-92. doi: 10.1074/jbc. M802240200 PMID: 18420577
21. Kuo M, Zilberfarb V, Gangneux N, Christeff N, Issad T. O-glycosylation of FoxO1 increases its transcriptional activity towards the glucose 6-phosphatase gene. FEBS Letters 2008; 582(5):829-34. doi: 10.1016/j.febslet.2008.02.010 PMID: 18280254
22. Yang J, Kalhan SC, Hanson RW. What is the metabolic role of phosphoenolpyruvate carboxykinase J Biol Chem 2009; 284(40):27025-9. doi: 10.1074/jbc.R109.040543 PMID: 19636077
23. Blake WL, Clarke SD. Induction of adipose fatty acid binding protein (a-FABP) by insulin-like growth factor-1 (IGF-1) in 3T3-L1 preadipocytes. Biochem Biophys Res Commun 1990; 173(1):87-91. PMID: 1701639
24. Hresko RC, Hoffman RD, Flores-Riveros JR, Lane MD. Insulin receptor tyrosine kinase-catalyzed phosphorylation of 422(aP2) protein. Substrate activation by long-chain fatty acid. J Biol Chem 1990; 265(34):21075-85. PMID: 2174434
25. Martin GG, Atshaves BP, Landrock KK, Landrock D, Schroeder F, Kier AB. Loss of L-FABP, SCP-2/SCP-x, or both induces hepatic lipid accumulation in female mice. Arch Biochem Biophys 2015; 580:41-9. doi: 10.1016/j.abb.2015.06.009 PMID: 26116377
26. Guzman C, Benet M, Pisonero-Vaquero S, Moya M, Garcia-Mediavilla MV, Martinez-Chantar ML, et al. The human liver fatty acid binding protein (FABP1) gene is activated by FOXA1 and PPARalpha; and repressed by C/EBPalpha: Implications in FABP1 down-regulation in nonalcoholic fatty liver disease. Biochim Biophys Acta 2013; 1831(4):803-18. doi: 10.1016/j.bbalip.2012.12.014 PMID: 23318274
27. Le TT, Ziemba A, Urasaki Y, Hayes E, Brotman S, Pizzorno G. Disruption of uridine homeostasis links liver pyrimidine metabolism to lipid accumulation. J Lipid Res 2013; 54(4):1044-57. doi: 10.1194/jlr. M034249 PMID: 23355744
28. Wurtman RJ, Regan M, Ulus I, Yu L. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol 2000; 60(7):989-92. PMID: 10974208
29. Gasser T, Moyer JD, Handschumacher RE. Novel single-pass exchange of circulating uridine in rat liver. Science 1981; 213(4509):777-8. PMID: 7256279
30. van Groeningen CJ, Peters GJ, Nadal JC, Laurensse E, Pinedo HM. Clinical and pharmacologic study of orally administered uridine. J Natl Cancer Inst 1991; 83(6):437-41. PMID: 1999851
31. Hart GW, Slawson C, Ramirez-Correa G, Lagerlof O. Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. Ann Rev Biochem 2011; 80:825-58. doi: 10.1146/annurev-biochem-060608-102511 PMID: 21391816
32. Gual P, Le Marchand-Brustel Y, Tanti JF. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie 2005; 87(1):99-109. PMID: 15733744
33. Begriche K, Massart J, Robin MA, Borgne-Sanchez A, Fromenty B. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol 2011; 54(4):773-94. doi: 10.1016/j.jhep.2010.11.006 PMID: 21145849
34. Zhang Y, Repa JJ, Inoue Y, Hayhurst GP, Gonzalez FJ, Mangelsdorf DJ. Identification of a liver-specific uridine phosphorylase that is regulated by multiple lipid-sensing nuclear receptors. Mol Endocrinol 2004; 18(4):851-62. PMID: 14715930
35. Pizzorno G, Yee L, Burtness BA, Marsh JC, Darnowski JW, Chu MY, et al. Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor. Clin Cancer Res 1998; 4 (5):1165-75. PMID: 9607574
36. Cao D, Leffert JJ, McCabe J, Kim B, Pizzorno G. Abnormalities in uridine homeostatic regulation and pyrimidine nucleotide metabolism as a consequence of the deletion of the uridine phosphorylase gene. J Biol Chem 2005; 280(22):21169-75. PMID: 15772079
37. Roosild TP, Castronovo S, Villoso A, Ziemba A, Pizzorno G. A novel structural mechanism for redox regulation of uridine phosphorylase 2 activity. J Struct Biol 2011; 176(2):229-37. doi: 10.1016/j.jsb. 2011.08.002 PMID: 21855639