Accelerated loss of lean body mass in fasting rats due to activation of pyruvate dehydrogenase by dichloroacetate

Abstract

In order to test the hypothesis that increased pyruvate dehydrogenase (PDH) activity during fasting will result in accelerated loss of lean body mass, we administered sodium dichloroacetate (DCA) intraperitoneally to eight rats during the last three days of a six-day fast, while fasting control rats were given normal saline. DCA treatment resulted in an increased proportion of PDH in the active form in liver (26.5 +/- 4.3% v 13.4 +/- 0.5%, P less than 0.01). During the three-day period of administration, DCA treated rats lost more weight than control animals (42 +/- 2 v 25 +/- 1 g, P less than 0.001) and excreted more nitrogen in the urine (18.1 +/- 1.0 v 6.8 +/- 0.6 mmol/d, P less than 0.001). Calculations from nitrogen balance data suggest that 85% of the increase in weight loss of DCA treated rats over that of control animals was attributable to loss of lean body mass. We conclude that increased flux of pyruvate through the PDH reaction in the DCA-treated animals resulted in increased protein catabolism.