Effects of carnitine on medium-chain fatty acid metabolism in newborn pigs

Metabolism of medium-chain fatty acids (MCFA) is considered to be independent of carnitine because of their passive diffusion into the mitochondrion. However, upon feeding medium-chain triglycerides (MCT) to piglets (n = 16) followed by serial blood sampling, we observed significant changes in free and acyl-carnitines in plasma as determined using a newly developed HPLC procedure which allows for quantification of individual carnitine esters. The most noticeably change was observed in propionyl-carnitine, which increased significantly (from 0 to 4μM, p $<$.05) upon feeding odd-chain MCT, while it was undetectable when even-chain MCT were fed. This suggests a role for carnitine, likely mediated via buffering the acyl-CoA/free CoA ratio in the mitochondria since propionyl-esters under the conditions employed are mainly produced inside the mitochondrion. To further investigate whether carnitine alters MCFA oxidation in vivo, we infused pigs (n = 34) continuously with MCFA via umbilical arterial catheters; and after an adaptation period, carnitine was added to the infusate. The addition of carnitine increased MCFA oxidation (p $<$.01) when MCFA oxidation provided more than 20% of the metabolic energy (increase = 0.16$\cdot$(fatty acid oxidation rate $-$ 18), r = 0.74, p $<$.01). In addition, in 18 of these pigs, dicarboxylic acid (DCA, analyzed using HPLC) excretion in urine (collected via a bladder catheter inserted via the umbilicus) was measured over time. Carnitine supplementation decreased DCA excretion by 45% (p $<$ 0.05) in urine. This suggests that carnitine lowered the intracellular fatty acid concentration in the liver (possibly due to an increased fatty acid oxidation) since DCA production is correlated with the fatty acid concentration. Carnitine supplementation also increased plasma and liver carnitine and acetyl-carnitine concentrations and urinary acetyl-carnitine excretion. However, no increase was observed in muscle acetyl-carnitine. The increase in liver acetyl-carnitine due to carnitine and fatty acid infusion concurs with the hypothesis that carnitine acts as a buffer to the hepatic intramitochondrial acyl-CoA/CoA ratio, aiding in the export of excess acyl groups and thereby, relieving the mitochondrion of a toxic substance which is capable of inhibiting oxidative processes as well as the urea cycle.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Agriculture, Animal Culture and Nutrition

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• van Kempen, Theo A.T.G.

Contributors dc:contributor

• Odle, Jack

• Agriculture, Animal Culture and Nutrition
• Health Sciences, Nutrition

Statement dc:rights

• Copyright 1993 van Kempen, Theo A. T. G.

Language dc:language

eng

Identifier

AAI9411808
(UMI)AAI9411808

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/23606