[Parenterally administered medium-chain triglyceride-induced changes in carnitine metabolism]. / Parenteral verabreichte mittelkettige Triglyzeride induzieren Veränderungen im Carnitin-Stoffwechsel.

Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate was studied in four healthy male adults. Glucose and amino acids were infused alone for three hours, then continued for another 5.5 hours together with a lipid emulsion containing only long-chain triglycerides or a mixture of medium-chain and long-chain triglycerides (50:50; w/w). During the fat-free infusion, the concentration of free carnitine rose, while the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 hours reduced free carnitine to lower values (32.4 +/- 4.7 mumols/L) than long-chain triglycerides infusion (44.4 +/- 2.7 mumols/L). By contrast, the plasma concentrations of short-chain acylcarnitines (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/L; p less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/L; p less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. These findings suggest that oxidation of medium-chain fatty acids is to some extent carnitine-dependent, whether or not transport into mitochondria is carnitine-mediated.

Mechanisms of starvation diabetes: a study with double tracer and indirect calorimetry.

To analyze the mechanisms of fasting-induced glucose intolerance, glucose metabolism was studied before and after the ingestion of 75 g glucose in 24 normal subjects fasted for either 14 h (n = 12) or 4 days (n = 12). The techniques included intravenous infusion of [6-3H]glucose and oral administration of [1-14C]glucose combined with indirect calorimetry. Compared with the controls, the starved subjects exhibited the following differences in glucose metabolism during the 5 h after glucose ingestion. 1) Mean incremental levels were fourfold higher for glucose and 40% higher for insulin. 2) Absorption of oral glucose was delayed and prolonged, but total amount reaching systemic circulation in 5 h was identical in the two groups (approximately 63 g). 3) Suppression of hepatic glucose output was reduced (-12 +/- 1 vs. -22 +/- 2 g). 4) Consequently, the increment in peripheral appearance of total glucose (exogenous plus endogenous) was augmented (+ 52 +/- 2 vs. +41 +/- 2 g). 5) Mean glucose clearance increased significantly less (+28 +/- 7 vs. +96 +/- 10 ml/min). 6) Oxidation of oral glucose was reduced (9 +/- 2 vs. 36 +/- 3 g), and nonoxidative disposal (presumably storage) was enhanced (56 +/- 2 vs. 36 +/- 3 g) in the presence of an elevated fat oxidation (35 +/- 2 vs. 22 +/- 4 g). Thus the alterations in glucose homeostasis responsible for the starvation-induced glucose intolerance are located both at the splanchnic (hepatic) and peripheral levels.

Medium-chain triglycerides induce alterations in carnitine metabolism.

Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate were studied in four healthy male adults. Glucose and amino acids were infused alone for 3 h, then continued for another 5.5 h together with a lipid emulsion containing only long-chain triglycerides or a 50:50% (wt/wt) mixture of medium-chain and long-chain triglycerides. During the fat-free infusion, the concentration of free carnitine rose, whereas the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 h reduced free carnitine to lower values (32.4 +/- 4.7 mumols/l) than long-chain triglycerides infusion (44.4 +/- 2.7 mumol/l). By contrast, the plasma concentrations of short-chain acylcarnitine (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/l; P less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/l; P less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. This suggests that intravenous medium-chain triglycerides are not metabolized independently of carnitine. Carnitine may play an important role in removing acyl and acetyl groups from mitochondria and in restoring the intramitochondrial CoA level. Fat substrates are converted into compounds that might be utilized by tissues that do not normally oxidize fatty acids, creating an interorgan energy cycle.