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Hepatic ATP and Triglyceride Levels in Choline-deficient Rats with and without Dietary Orotic Acid Supplementation¹

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut

Hepatic ATP depletion is probably important in the pathogenesis of the experimental fatty livers produced by orotic acid and several other agents that inhibit hepatic lipoprotein production. Because choline deficiency also impairs lipoprotein production, we have investigated the role of ATP depletion in this condition. Rats fed a choline-deficient diet for 5 days had no change in hepatic ATP despite a 30-fold increase in triglycerides. Furthermore, adenine sulfate, an ATP precursor, failed to influence the degree of lipid accumulation when added to the diet. In contrast, adding 1% orotic acid to a choline-supplemented diet for 5 days produced a 50% fall in ATP along with a sevenfold increase in hepatic triglycerides, and 0.25% dietary adenine sulfate completely prevented both these effects. A previously reported protective effect of orotic acid in choline deficiency was confirmed by the fact that choline-deficient rats fed orotic acid had about 50% lower hepatic triglyceride levels than those not given this agent. Despite this, orotic acid lowered ATP in choline-deficient animals equally as well as in choline-supplemented animals. These results indicate that unlike the lipid accumulation induced by orotic acid, the fatty liver of choline deficiency is not related to hepatic ATP depletion. The paradoxical protective effect of orotic acid in choline deficiency appears to be independent of its influence on ATP.

Manuscript received 13 February 1969.

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