Administration of dichloroacetate (DCA) to normal rats resulted in a fall in serum glucose and triglycerides and a rise in ketone bodies. Insulin and cholesterol levels were unchanged. The effects of DCA on lipid metabolism were examined in isolated rat hepatocytes. At 10 mM DCA, the incorporation of tritiated water into fatty acids (saponifiable lipids) was inhibited by 33 ± 4% (mean ± SEM, N = 5). No effect on incorporation into cholesterol (measured as nonsaponifiable lipids) was observed. DCA inhibited the incorporation of 14C-glucose into lipid but had no effect on glucose oxidation. Fatty acid oxidation was increased by 76 ± 7% (mean ± SEM, N = 6). However, DCA had no effect on the recovery of newly synthesized lipid. Thus, inhibition of tritiated water incorporation into fatty acids represents decreased synthesis rather than increased turnover. DCA did not affect the incorporation of 14C-palmitate into triglycerides or phospholipids. Cell viability, as assessed by incorporation of 3H-isoleucine into protein and trypan blue exclusion, was not affected by DCA. These results suggest that DCA lowers serum triglycerides through inhibition of fatty acid synthesis and stimulation of fatty acid oxidation by liver.

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