Calcitonin and Hepatic Fatty Acid Synthesis: Effect of Thyroparathyroidectomy on the Elevation of ATP Citrate Lyase Activity by Refeeding of Starved Rats

Summary

The effect of thyroparathyroidectomy (TPTX) on ATP citrate lyase regulation, a rate-limiting enzyme of fatty acid synthesis in hepatic cytosol, was investigated in rats refed after a 24 h fast. ATP citrate lyase activity in the hepatic cytosol was increased 2-fold by refeeding. This increase was supressed about 50 % by TPTX. The supression of the enzyme activity by TPTX was completely restored by administration of calcitonin (CT; 80 MRC mU/100 g body weight). This hormonal effect was also observed at 20 MRC mU/100 g dose of CT. CT administration to refeeding-TPTX rats produced a significant increase in the calcium content of the liver tissue and the cytosol. The cytosolic ATP citrate lyase activity increase with CT administration was completely blocked by treatment of cytosol with EGTA (10 μM). This inhibition was clearly reversed by addition of calcium ion (1.25-5.0 μM). In addition, CT-induced rise in enzyme activity was markedly reduced by the presence of W-7 (5 and 50 μM), a calmodulin inhibitor, in the enzyme assay system. The present results suggest that CT plays a role in the elevation of hepatic ATP citrate lyase activity brought about by refeeding of fasted rats, and that this hormonal regulation might depend on Ca²⁺-calmodulin.

Key-Words

Calcitonin - ATP Citrate Lyase - Calcium - Calmodulin - Thyroparathyroidectomized Rats - Refeeding Fasted Rats