Calcitonin and hepatic fatty acid synthesis: effect of thyroparathyroidectomy on the elevation of ATP citrate lyase activity by refeeding of starved rats.

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 suppressed about 50% by TPTX. The suppression 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 microM). This inhibition was clearly reversed by addition of calcium ion (1.25-5.0 microM). In addition, CT-induced rise in enzyme activity was markedly reduced by the presence of W-7 (5 and 50 microM), 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.

Calcitonin increases fatty acid synthetase activity dependently of calcium-calmodulin in the hepatic cytosol of fed rats.

The effect of calcitonin (CT) on fatty acid synthetase activity in the hepatic cytosol was investigated after a single subcutaneous administration of the hormone to fed rats. Administration of CT (synthetic [Asu1,7] eel CT; 80 MRC mU/100 g body weight) produced significant increases in fatty acid synthetase activity and calcium concentration in the hepatic cytosol of intact and thyroparathyroidectomized rats. The hormonal effect on the enzyme activity was not observed in rats fasted for 24 h. The increase in fatty acid synthetase activity by CT administration was completely inhibited by treatment with 10 microM EGTA. This enzyme activity was restored by addition of calcium ion (2.5-10 microM). The increased enzyme activity of CT-treated rats was markedly reduced by addition of W-7 (15 microM), a calmodulin inhibitor, in the enzyme assay system. Moreover, the cytosolic enzyme activity of normal rat liver was markedly raised by in vitro addition of both calcium ion (5 microM) and calmodulin (2.5 micrograms). These results suggest that CT increases fatty acid synthetase activity in the hepatic cytosol of fed rats, and that this hormonal regulation may depend on calmodulin, and be mediated through raised calcium in the cytosol.