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TRANSLATIONAL PHYSIOLOGY

Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats

Departments of ¹Pediatrics and ²Nutrition, Case Western Reserve University, Cleveland, Ohio; ³Fachhochschule Lippe und Hoxter University of Applied Sciences, Detmold, Germany; ⁴Sasol GmbH, Witten, Germany; and ⁵Institute of Metabolic Disease, Baylor University Medical Center, Dallas, Texas

Submitted 5 August 2005 ; accepted in final form 8 May 2006

A new chronic treatment for inherited disorders of long-chain fatty acid oxidation involves administering up to one-third of dietary calories as triheptanoin, a medium-odd-chain triglyceride (Roe CR, Sweetman L, Roe DS, David F, and Brunengraber H. J Clin Invest 110: 259–269, 2002). Heptanoate and C₅-ketone bodies derived from its partial oxidation in liver are precursors of anaplerotic propionyl-CoA in peripheral tissues. It was hypothesized that increasing anaplerosis in peripheral tissues would boost energy production. In the present study, we tested the potential of a triheptanoin emulsion as an intravenous nutrient. Normal rats were infused with triheptanoin intravenously or intraduodenally at up to 40% of caloric requirement. The blood concentration ratio (heptanoate/C₅-ketone bodies) was high with intravenous and low with intraduodenal triheptanoin infusion. During intravenous infusion of triheptanoin, lipolysis was stimulated but appeared compensated by fatty acid reesterification. During intraduodenal infusion of triheptanoin, lipolysis was not stimulated. Our data support the hypothesis that intravenous triheptanoin could be used to treat decompensated patients with long-chain fatty acid oxidation disorders.

heptanoate; C₅-ketone bodies; fatty acid oxidation disorders; anaplerosis

This article has been cited by other articles:

				L. Gu, G.-F. Zhang, R. S. Kombu, F. Allen, G. Kutz, W.-U. Brewer, C. R. Roe, and H. Brunengraber Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile Am J Physiol Endocrinol Metab, February 1, 2010; 298(2): E362 - E371. [Abstract] [Full Text] [PDF]

				C. R. Roe, B-Z Yang, H. Brunengraber, D. S. Roe, M. Wallace, and B. K. Garritson Carnitine palmitoyltransferase II deficiency: Successful anaplerotic diet therapy Neurology, July 22, 2008; 71(4): 260 - 264. [Abstract] [Full Text] [PDF]