Sodium pivalate treatment reduces tissue carnitines and enhances ketosis in rats

Sodium pivalate, a compound conjugated to carnitine and excreted in the urine was used to induce a secondary carnitine deficiency. In the first series of experiments, rats received in their drinking water either 20 mmol/L sodium pivalate (experimental) or 20 mmol/L sodium bicarbonate (control) for 4 d, 2 wk, or 8 wk. Tissues and urine were collected, and carnitine concentrations in liver, skeletal muscle, heart, plasma and urine were determined. The total carnitine concentrations in tissues and plasma of pivalate-treated rats were significantly depressed (P less than 0.05) at all time points, except at 4 d for skeletal muscle and at 4 d and 2 wk for liver. The acylcarnitine:free carnitine ratios in urine and plasma of the pivalate-treated animals were significantly higher at all time points relative to the controls. In the second experiment, rats received either the pivalate or the bicarbonate treatments for 15 d followed by a 2-d fast. After fasting, the plasma beta-hydroxybutyrate of pivalate-treated rats was significantly higher relative to controls, but there was no significant difference in plasma glucose concentrations. The reduced plasma and tissue carnitine concentrations, increased acylcarnitine:free carnitine ratio in plasma and urine, and fasting ketosis found in pivalate-treated rats are findings also reported for human secondary carnitine deficiency due to organic acidurias.