Metabolism and metabolic effects of anaplerotic triheptanoin (TH) in normal rats

Anaplerotic TH (glycerol triheptanoate) is used for the chronic oral treatment of long-chain fatty acid oxidation disorders (FOD). To test whether TH could also be used for the acute intravenous treatment of decompensated FOD patients, we investigated the metabolism and metabolic effects of triheptanoin emulsion administered parenterally or enterally. Rats were infused with TH emulsion (intravenously or intragastrically). Stable isotope tracers were infused intravenously to measure the rates of appearance (Ra) of plasma glucose, glycerol and fatty acids. Surprisingly, intravenous infusion of triheptanoin markedly increased glycerol Ra but not oleate Ra. This indicated that massive lipolysis induced by intravenous TH was not accompanied by the release of long-chain fatty acids from adipocytes. This probably results from the contribution of anaplerotic propionyl-CoA moiety of heptanoate to glyceroneogenesis in adipocytes, generating sufficient amounts of glycerol-3-phosphate to re-esterify the fatty acids derived from stimulated lipolysis. The intraduodenal infusion of TH did not induce lipolysis because TH was hydrolyzed in the gut. Our data support the use of intravenous TH emulsion for the acute treatment of FOD patients (for whom the release of fatty acids from adipocytes would be harmful). Supported by NIH.