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

van Kempen, Theo A.T.G.

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https://hdl.handle.net/2142/23606 Copy

Description

Title

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

Author(s)

van Kempen, Theo A.T.G.

Issue Date

1993

Doctoral Committee Chair(s)

Odle, Jack

Department of Study

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

Discipline

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

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

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

Language

eng

Abstract

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 4$\mu$M, 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.

Type of Resource

text

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http://hdl.handle.net/2142/23606

Copyright and License Information

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

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