Perfusion in Situ with Tritium Oxide to Measure Hepatic Lipogenesis and Lipid Secretion

NORMAL AND OROTIC ACID-FED RATS

From the ¹ From the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland 20014

From measurements of tritium incorporation following the perfusion in situ of livers with blood enriched in ³H₂O, the rate of hepatic fatty acid and cholesterol biosynthesis in young nonfasted rats was found to be 7.0 and 0.09 µmoles per g of liver per hour, respectively. Newly synthesized fatty acids were utilized by liver in the same manner as has been shown by others for preformed fatty acids arriving in liver via plasma; at the end of 3 hours, 37% were found in liver phospholipids, 34% in liver neutral lipids, and 29% had been released into the perfusate, nearly all as triglycerides. At least two pools of liver triglycerides could be shown.

Depriving a rat of food for 48 hours reduced hepatic fatty acid and cholesterol synthesis to less than 2% the rate in nonfasted controls.

Feeding rats 1% orotic acid reduced hepatic fatty acid synthesis, stimulated cholesterolgenesis, and almost completely blocked the transfer of hepatic lipids into perfusate. From whole animal studies with Triton, the block in lipid secretion was found to increase in severity during the first week of orotic acid feeding, and could be rapidly reversed by inclusion of 0.25% dietary adenine sulfate. Accumulated liver triglyceride was seen only after 3 days of continuous orotic acid feeding.

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