Abstract
Feeding rats orotic acid as l o of a semisynthetic high sucrose diet induced a specific defect in hepatic lipid secretion and resulted in hepatic fatty degeneration. This inhibition of hepatic lipid secretion by ortic acid was investigated in rat primary cultured hepatocytes. The addition of 6.4 mM orotic acid to culture system within 20 hours decreased lipid secretion, triglyceride by 49%, phospholipid by 71%, and cholesterol by 81%. In the same experiment, cellular triglyceride decreased by 81%. Microscopic studies show the addition of orotic acid to increase extraordinary hepatocytes including Sudan III positive small lipid droplets. In orotic acid-treated groups, hepatocytes including Sudan III positive small lipid droplets increased in number. Ultrastructural studies demonstrated marked dilatation of Golgi apparatus during 20 hours incubation with orotic acid. This ultrastructual change means inhibition of lipid secretion by orotic acid. These observations indicate that in rat primary cultured hepatocytes, orotic acid induces lipid secretion as in animal experiments, both biochemically and pathologically.
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