EFFECT OF MEDIUM CHAIN TRIGLYCERIDE (MCT) ADMINISTRATION ON CARNITINE METABOLISM IN THE ANESTHESIZED PIGLET AND CULTURED KIDNEY EPITHELIAL CELLS

Abstract

To test the hypothesis that carnitine plays a role in medium chain fatty acid metabolism, blood, urine, liver and bile specimens were collected from anesthesized neonatal piglets prior to, and after 30, 60, 120 and 180 minutes of a continuous intravenous infusion of MCT (1 g/kg-h). Interval fractional tubular reabsorption was calculated throughout the infusion. 3H-L-Carnitine uptake was determined in cultured renal tubular epithelial (Cos-l) cells incubated with increasing amounts of octanoic acid.Results: The ketogenic response to MCT administration was associated with a rise in esterified (15.2-->40.9 μM), particularly acetylcamitine (11.4-->26.2 μM), and a fall in free carnitine plasma concentrations (34.6-->14.4 μM). The appearance in the plasma, bile and liver of butyryl-, hexanoyl-, octanoyl- and decanoylcarniune and the greater than 4-fold increase in ratios of plasma free fatty acids/β-hydroxybutyratc and lactate/pyruvate suggested overloading of both β- and Krebs cycle oxidative pathways. The fractional tubular reabsorption of free carnitine decreased from 96.5% to 48.7% with MCT loading, and was associated with a 6-fold increase of free carnitine excretion. Uptake of 3H-L-Carnitine into Cos-1 cells decreased in a dose-dependent manner with increasing octanoic acid concentration. The results suggest that MCT loading has profound effects on carnitine metabolism affecting intracellular esterifications and renal tubular reabsorption.