Plasma acylcarnitine concentrations reflect the acylcarnitine profile in cardiac tissues

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.

Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity

“…The concentrations of acylcarnitines in the plasma samples were determined with a UPLC MS/MS method using a Waters Acquity liquid chromatography system and Waters Quattro Micro or Waters Xevo TQ-S mass spectrometer, as previously described (17,27).…”

“…Long-chain acylcarnitines are formed in mitochondria from free L-carnitine and acyl-CoA moieties (14,15). Because longchain FAs are the main energy substrates in the skeletal muscles and the heart, these tissues are considered essential contributors to the long-chain acylcarnitine pool in plasma (16,17). Increased plasma levels of various acylcarnitines were found in experimental animal models of insulin resistance (16) and in patients with obesity, impaired glucose tolerance and type 2 diabetes (11,(18)(19)(20)(21)(22).…”

Remote ischaemic preconditioning influences the levels of acylcarnitines in vascular surgery: a randomised clinical trial

“…Hence plasma ACs does not exactly reflect whole-body acylcarnitine metabolism [16], but it allows to make some conclusions about metabolism in some organs. SCASs in plasma has been found to be released from the liver [16], MCACs, from the skeletal muscles and liver [17] and LCACs, from the heart [15]. It should be noted that the hepatoprotective effect of RIPC has been reported previously [4,18].…”

“…The main precursors of SCACs are branched chain amino acids (BCAAs) but some SCASs are also produced by catabolism of glucose and some triglycerides. MCACs and LCACS are only derived from fatty acid metabolism whereas carnitine is required for transporting long-chain fatty acids into mitochondria [15]. Hence plasma ACs does not exactly reflect whole-body acylcarnitine metabolism [16], but it allows to make some conclusions about metabolism in some organs.…”

Multiomics approach reveals metabolic changes in the heart at birth

“…Our lipidomic approach was able to identify two short-chain (AcCa 2:0 and AcCa 4:0), three medium-chain (AcCa 8:0, AcCa 10:0, and AcCa 12:0), and four long-chain acylcarnitines (AcCa 16:0, AcCa 16:0-OH/14:0, AcCa 18:0, and AcCa 18:1), with significant elevations in medium-and long-chain acylcarnitines in newborn cardiac tissue (Table 2). Medium-and long-chain acylcarnitines are produced from the breakdown of fatty acids in the mitochondria during ␤-oxidation and are abundant in cardiac tissue (38). A previous study in the bovine heart revealed that the fetal heart maintains the same ability to utilize short-and medium-chain fatty acids for oxidative phosphorylation as the neonatal heart but that longchain fatty acid metabolism is only present in neonatal cardiac mitochondria (64).…”