Plasma acylcarnitine concentrations reflect the acylcarnitine profile in cardiac tissues

Marina Makrecka-Kuka,Maija Dambrova,Eduards Sevostjanovs,Elina Makarova,Unigunde Antone,Osvalds Pugovics,Edgars Liepinsh,Karlis Vilks,Kristine Volska,Janis Kuka

doi:10.1038/s41598-017-17797-x

Marina Makrecka-Kuka, Maija Dambrova + Show 8 more

Open Access

https://doi.org/10.1038/s41598-017-17797-x

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Abstract

Increased plasma concentrations of acylcarnitines (ACs) are suggested as a marker of metabolism disorders. The aim of the present study was to clarify which tissues are responsible for changes in the AC pool in plasma. The concentrations of medium- and long-chain ACs were changing during the fed-fast cycle in rat heart, muscles and liver. After 60 min running exercise, AC content was increased in fasted mice muscles, but not in plasma or heart. After glucose bolus administration in fasted rats, the AC concentrations in plasma decreased after 30 min but then began to increase, while in the muscles and liver, the contents of medium- and long-chain ACs were unchanged or even increased. Only the heart showed a decrease in medium- and long-chain AC contents that was similar to that observed in plasma. In isolated rat heart, but not isolated-contracting mice muscles, the significant efflux of medium- and long-chain ACs was observed. The efflux was reduced by 40% after the addition of glucose and insulin to the perfusion solution. Overall, these results indicate that during fed-fast cycle shifting the heart determines the medium- and long-chain AC profile in plasma, due to a rapid response to the availability of circulating energy substrates.

Highlights

Acylcarnitines (ACs) are formed from carnitine and acyl-CoAs by carnitine acyltransferases in mitochondria or peroxisomes[1,2]
We demonstrated that the most pronounced difference in AC content between the fed and fasted states was observed in tissues that are metabolically flexible
We showed that the amount of ACs in plasma is comparable with the heart tissue content of long- and medium-chain ACs and it can be affected by a metabolic switch from fatty acid to glucose oxidation in the heart

Summary

Introduction

Acylcarnitines (ACs) are formed from carnitine and acyl-CoAs by carnitine acyltransferases in mitochondria or peroxisomes[1,2]. Since the metabolism of fatty acids, glucose and amino acids can yield ACs, their concentration in plasma is determined by the nutritional state and tissue- or organ-specific contributions. Measurements of ACs in fed and fasted states showed that the plasma long-chain AC concentration reflects the AC content in cardiac tissue, but the data regarding the content in muscles are controversial[15,16,17,26]. These data indicate that plasma ACs relationship to the tissue ACs could be dependent on the metabolic condition imposed at the time of assessment. The AC effluxes were measured in isolated organ models

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