Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile

1 Department of Nutrition, Case Western Reserve University, Cleveland, Ohio; 2 Hochschule Ostwestfalen-Lippe University of Applied Sciences, Detmold; 3 Sasol GmbH, Witten, Germany; and 4 Depertment of Neurology, University of Texas Southwestern, Dallas, Texas Submitted 16 June 2009 ; accepted in final form 6 November 2009 The anaplerotic odd-medium-chain triglyceride triheptanoin is used in clinical trials for the chronic dietary treatment of patients with long-chain fatty acid oxidation disorders. We previously showed (Kinman RP, Kasumov T, Jobbins KA, Thomas KR, Adams JE, Brunengraber LN, Kutz G, Brewer WU, Roe CR, Brunengraber H. Am J Physiol Endocrinol Metab 291: E860–E866, 2006) that the intravenous infusion of triheptanoin increases lipolysis traced by the turnover of glycerol. In this study, we tested whether lipolysis induced by triheptanoin infusion is accompanied by the potentially harmful release of long-chain fatty acids. Rats were infused with heptanoate ± glycerol or triheptanoin. Intravenous infusion of triheptanoin at 40% of caloric requirement markedly increased glycerol endogenous R a but not oleate endogenous R a . Thus, the activation of lipolysis was balanced by fatty acid reesterification in the same cells. The liver acyl-CoA profile showed the accumulation of intermediates of heptanoate β-oxidation and C 5 -ketogenesis and a decrease in free CoA but no evidence of metabolic perturbation of liver metabolism such as propionyl overload. Our data suggest that triheptanoin, administered either intravenously or intraduodenally, could be used for intensive care and nutritional support of metabolically decompensated long-chain fatty acid oxidation disorders. Address for reprint requests and other correspondence: H. Brunengraber, Dept. of Nutrition, Case Western Reserve University, School of Medicine, WG-48, 10900 Euclid Ave., Cleveland, OH 44106-4954 (e-mail: hxb8{at}case.edu ).