Uridine prevents fenofibrate-induced fatty liver.
Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD(+)/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD) and acyl-CoA oxidase 1 (ACOX1), and induces excessive accumulation of long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA). Uridine co-administration at a daily dosage of 400 mg/kg raises NAD(+)/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver.
Nevada Cancer Institute, Las Vegas, Nevada, United States of America ; Desert Research Institute, Las Vegas, Nevada, United States of America.
Thuc T
TT
Le
Nevada Cancer Institute, Las Vegas, Nevada, United States of America ; Desert Research Institute, Las Vegas, Nevada, United States of America.
Yasuyo
Y
Urasaki
Nevada Cancer Institute, Las Vegas, Nevada, United States of America ; Desert Research Institute, Las Vegas, Nevada, United States of America.
Giuseppe
G
Pizzorno
D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D011345:Fenofibrate / Q000009:adverse effects*; D005786:Gene Expression Regulation; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D063994:Peroxisomal Bifunctional Enzyme / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D014529:Uridine / Q000494:pharmacology*
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D020011:Protective Agents; D009243:NAD; D042962:Acyl-CoA Oxidase; D063994:Peroxisomal Bifunctional Enzyme; D011345:Fenofibrate; D014529:Uridine