ABSTRACT
The present study was conducted to elucidate the metabolic pathways by which enlarged liver size of patients undergoing disorders of orotic acid de novo metabolism and those patients of enlarged liver size induced by di(2-ethyl hexyl) phthalate in rats as animal model. The results showed that rats-treated with orotic acid generated liver triglyceride content 400% higher than that of the control accompanied with a significant decrease of phospholipid levels (P<0.05). The rates of lipogenic enzymes, both fatty acid synthase (FAS) and phosphatidate phosphohydrolase (PAP), increase accompanying promotions of liver triglyceride content without any changes in fatty acid degradation pathway. However, those rats-treated with di(2- ethyl hexyl) phthalate generated liver phospholipid level significantly higher than of the control accompanied with a markedly decreased the liver triglyceride levels. Both FAS and PAP activities were almost similar with those controls but the rates of fatty acid degradation were increased approximately by 2.5-fold of control. In conclusion: The enlargement of liver size induced by orotic acid is associated with largely retains triglyceride molecules in liver tissues, whereas those induced by di(2-ethyl hexyl) is associated with the induction of phosphorylation generating an increase of liver phospholipid levels.
ABSTRACT
Aim: Objectives To evalate the differences in metabolic responses between dietary orotic acid and adenine in lipid profi les of serum and liver tissues. Methods: Rats were paired-fed 1.0 % orotic acid (orotic acid group) and 0.25 % adenine (adenine group) diets or a non-supplemented diet (control group) for 10 days. Serum lipid concentrations were measured using enzyme assay kits. Lipids of liver tissues were extracted and the lipid contents were determined. Results: Serum lipid concentrations (in mg/dL) of adenine group tended to increase whereas those levels decreased in orotic acid group compared to control group. The serum triglyceride (TG) concentrations of control, orotic acid, and adenine groups were (78.1±14.9), (69.0±23.6), and (136.1±21.6); phospholipids (PL): (109.2±11.5), (93.3±10.5), and (131.3±11.0); total cholesterol: (53.7±4.6), (42.9±6.5), and (68.1±5.8); and high-density lipoprotein (HDL)-cholesterol: (35.4±2.7), (33.0±3.0), and (44.7±2.7), respectively. Furthermore, liver TG content of orotic acid group markedly increased. The increase was approximately by 10-fold in comparison to other groups (P<0.05). The lipid contents of liver tissues (in mg/g tissue) in ordinarily of those three groups for TG were (11.4±1.3), (123.5±15.2), and (11.9±1.2); PL: (27.1±0.8), (25.4±1.3), and (30.7±0.6); and the total cholesterol: (2.73±0.09), (2.34±0.12), and (2.91±0.08), respectively. The liver PL and cholesterol content of adenine group increased by 21% and 25% than that of orotic acid group, but both lipid levels of the latter group increased by 7% and 15%, respectively, than that of the control group. Conclusion: Dietary adenine enhances the serum TG, PL, cholesterol, and HDL-cholesterol and the liver PL and cholesterol but without alters the liver TG levels. Dietary orotic acid, however, attenuates these serum lipid levels but retains those lipids synthesized in liver cells, mainly TG.